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Cellular Physiology
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470
Physiology
Graduate
08/23/2011

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Term
What is most abundant in cell membrane?
Definition
Phospholipids.
Term
What is the cell membrane made of?
Definition
Lipids and proteins.
Term
What does amphipathic mean?
Definition
Containing polar and nonpolar regions.
Term
What does cholesterol do?
Definition
It stiffens membranes and decreases membrane permeability to small water soluble molecules.
Term
What do glycolipids do?
Definition
Negatively charged ones increase the concentration of cations at the membrane surface; some act as receptors for bacterial toxins.
Term
What does it mean that the lipid distribution in bilayer is asymmetric?
Definition
glycolipids and choline-containing phospholipids only present on non-cytoplasmic side of membrane while phospholipids with terminal primary amine group are on cytoplasmic surface.
Term
Name the different type of membrane proteins.
Definition
Integral proteins, peripheral proteins, glycoproteins.
Term
Name some functions of integral proteins.
Definition
receptors, pores, channels, carriers, enzymes, adhesion molecules, intracellular signalling.
Term
What are peripheral proteins used for?
Definition
The formation of a submembranous cytoskeleton.
Term
What are glycoproteins involved with?
Definition
cell-cell interactions, receptors for viruses, antigenic determinants, cell surface negativity.
Term
What is glycocalyx?
Definition
carbohydrate rich coating of cells formed by glycolipids and glycoproteins.
Term
What is the function of the glycocalyx?
Definition
protect cell from mechanical and chemical damage; enables cells to identify and interact with one another.
Term
Are lipids and proteins mobile in cell membrane?
Definition
Yes. Can freely move in the plane of the membrane.
Term
What are the functions of biological membranes?
Definition
permeability barrier for water-soluble substances, forms cell organelles, and packages and transports materials within cells.
Term
What is endocytosis?
Definition
uptake of extracellular material in membrane bound vesicles. requires energy.
Term
What is phagocytosis?
Definition
a triggered process; uptake of large particulate matter; first bind to receptors on cell surface; vesicles are large; only some cells capable of it (e.g. macrophages and neutrophils)
Term
What are the receptors for phagocytosis?
Definition
Fc receptors for Fc portion of antibodies bound to pathogens, complement receptors, receptors that recognize oligosaccharides on surface of some microoorganisms, and presence of phosphatidylserine on apoptotic cells triggers phagocytosis.
Term
What is pinocytosis?
Definition
fluid filled endocytosis, a non-triggered process.; occurs at membrane sites coated with clathrin; constitutive process occuring in almost all cells; vesicles are small.
Term
What is receptor-mediated endocytosis?
Definition
uptake of specific substances bound to membrane receptors.; receptors gather in clathrin coated regions (coated pits), go through endocytosis, lose clathrin coat and ligand is released.
Term
What is caveolae endocytosis?
Definition
clathrin-independent endocytosis; small invaginations of ell membrane called caveolae occur at membrane sites rich in cholesterol and sphingomyelin (lipid rafts) which contain caveolin; caveolae pinch off to make vesicle and transport large molecules to plasma membrane on other side of cell = transcytosis.
Term
What is exocytosis?
Definition
Discharge of intracellular materials contained in membrane-bound vesicles. requires energy. primary method by which neurotransmitters, hormones, etc. are secreted.
Term
What is diffusion?
Definition
movement of atoms, molecules, or ions from one location to another as a result of their random, thermal motion.
Term
What is net diffusion?
Definition
movement of a substance from a region of higher concentration to region of lower concentration as a result of random movement.
Term
Explain Fick's first law of diffusion.
Definition
in a continuous system, the rate of diffusion across a planar surface is directly proportional to the area of the plane and the concentration gradient across the plane.
Term
Explain the Fick equation.
Definition
J = -DA (dc/dx), where J = net rate of diffusion in moles or grams per unit time; A = area of the plane; dc/dx = concentration gradient across the plane; D = diffusion coefficient
Term
What is the diffusion coefficient proportional to?
Definition
The speed at which a substance moves through the surrounding medium.
Term
At a small distance, diffusion is what?
Definition
Fast.
Term
When diffusing molecules don't interact with the barrier, describe the Fick equation.
Definition
J = -DA(change in C)/(change in X), where change in C = the concentration gradient across the barrier, and change in X = thickness of the barrier.
Term
What is one of the most important factors that determines how quickly a substance will move across cell membranes?
Definition
Lipid solubility.
Term
What is the partition coefficient?
Definition
That which measures the lipid solubility of a substance: Bi = [i]oil/[i]water, where Bi = partition coefficient of i, [i]oil = concentration of i in oil, [i]water = concentration of i in water.
Term
What are the properties of water?
Definition
distilled water is 55.55 molar; solute molecules displace water molecules and decrease water concentration; water tends to flow from region of high water concentration (low solute) to regions of low water concentration (high solute).
Term
What is an osmole?
Definition
the number of osmotically active particles in a solution? for salts, dissociation must be taken into account.
Term
What is osmolarity?
Definition
The number of osmoles/liter of solution.
Term
What is osmolality?
Definition
The number of osmoles/kg of water.
Term
What is osmosis?
Definition
The movement of water across a semipermeable membrane down its concentration gradient.
Term
What is osmotic pressure created by?
Definition
The difference in the concentration of impermeant substances across a semipermeable membrane.
Term
What is osmotic pressure?
Definition
That pressure which just counterbalances the movement of water into the solution.
Term
What does the osmotic pressure depend on?
Definition
the number of solute particles present.
Term
Name some colligative properties.
Definition
Osmotic pressure, freezing point depression, vapor pressure depression and boiling point elevation.
Term
van't Hoff law.
Definition
osmotic pressure = RTnc, where R = ideal gas constant (0.0821 atm*K-1mole-1), T = absolute temperature (K), c = molar concentration of solute (moles of solute/liter) and n = number of particles formed by dissociation of a solute molecule.
Term
Compare osmotic pressures.
Definition
Equal = isosmotic; higher = hyperosmotic; lower = hypoosmotic.
Term
What is tonicity.
Definition
A solution's ability to influence the volume of cells immersed in it.
Term
Why is cell volume only a reflection of the concentration of solutes in the extracelular solution compared with the solute concentration intracellularly?
Definition
Plasma membranes are relatively impermeable to most biological solutes but highly permeable to water.
Term
Compare the tonicity of solutions.
Definition
Isotonic = equal
Hypertonic = higher; cell shrinks
Hypotonic = lower; cell swells and lyses
Term
What happens when you add permeant solutes to physiological solutions?
Definition
Only transient change in cell volume occur.
Term
What happens when you place cells in solutions with only permeant solutes?
Definition
Cell lysis.
Term
What is the reflection coefficient?
Definition
the measure of the permeability of a membrane to a solute.
Term
What is the range of the reflection coefficient and what does it mean?
Definition
0 to 1; 0 = extremely permeable; 1 = impermeable
Term
What is bulk flow?
Definition
Movement of ions, molecules and particles in the same direction as a result of some force acting on them.
Term
Give an example of bulk flow.
Definition
Blood flow within blood vessels.
Term
What is ultrafiltration?
Definition
Separation by size, of solutes achieved by forcing the solution through a filter.
Term
Where does ultrafiltration occur?
Definition
Capillary beds.
Term
What is carrier mediated transport?
Definition
Movement of substances across the plasma membrane by protein carrier molecules (integral membrane proteins).
Term
Explain the model of carrier mediated transport.
Definition
Molecule can't cross or crosses membrane very slowly.
Carrier molecules have site which specifically binds molecule.
Molecule binding to site promotes conformational change, molecule is transported. No channel made.
Term
What is saturation?
Definition
When the rate of transport reaches its maximum as the concentration of transported substance increases; due to fixed and limited number of transporters in membrane.
Term
What are the properties of mediated transport?
Definition
Saturation, specificity and competition.
Term
Explain specificity.
Definition
Each carrier molecule binds to only a select group of substances but it's not absolute.
Term
Explain competition.
Definition
Since specificity isn't absolute, structurally related molecules can compete for transporter, decreasing rate of transport.
Term
What can inhibit transport?
Definition
Substances not structurally related to transported ion or molecule.
Term
Give an example of inhibition.
Definition
ATPases are inhibited by metabolic poisons that stop production of ATP.
Term
What is facilitated diffusion?
Definition
Protein carrier-mediated transport of substances down a concentration gradient; bidirectional.
Term
What is active transport?
Definition
Protein carrier-mediated transport of substances against a gradient; requires energy; unidirectional.
Term
What are the types of active transport?
Definition
Primary and secondary.
Term
Expplain primary active transport.
Definition
ATP hydrolysis supplies energy to transporter.
Term
Give an example of primary active transport.
Definition
Na-K ATPase.
Term
Explain secondary active transport.
Definition
Energy for transport isn't provided directly by ATP hydrolysis by indirectly by using existing gradient of an ion (Na).
Term
What is a uniport?
Definition
Transporter that transports only one substance at a time.
Term
Give an example of a uniport.
Definition
Facilitated diffusion of glucose.
Term
What is cotransport?
Definition
Symport transport; carrier has at least two sites; can transport substances in same direction.
Term
What transporters use cotransport and countertransport?
Definition
Secondary active transporters.
Term
Give an example of cotransport.
Definition
Na cotransport of amino acids.
Term
What is countertransport.
Definition
Antiport exchangers; carrier has at least two sites; all sites must be occupied; substances move in opposite directions.
Term
Give an example of countertransport.
Definition
Na-Ca exchanger.
Term
Explain Ca transport.
Definition
Present to help maintain low levels of intracellular free Ca.
Term
What are the type of Ca pumps?
Definition
SERCA and PMCA.
Term
What is SERCA?
Definition
Sarcoplasmic and Endoplasmic Reticulum Calcium ATPases; located on membranes of intracellular organelles; actively sequester Ca in intracellular stores.
Term
What is PMCA?
Definition
Plasma Membrane Calcium ATPases; play a major role in maintaining low intracellular Ca; inactive at physiologic [Ca], but when [Ca] increases, calcium combines with calmodulin (CaM) and that binds to pumpk, icnreasing affinity for Ca, as [Ca] decreases, Ca and CaM dissociate and pump is inactive.
Term
Explain H transport.
Definition
Occurs in parietal cells of gastric mucosa; transporter is H-K ATPase which transports H into gastric lumen and K into pareital cell.
Term
What do anion exchangers do?
Definition
Exchange extracellular univalent anions for intracellular ones.
Term
Give an example of an anion exchanger.
Definition
Chloride-bicarbonate exchanger.
Term
Explain Na-K-2Cl transporter.
Definition
Found in variety of nonepithelial cells and basolateral membrane of some epithelial cells; one function is regulation of cell volume.
Term
What are ABC transporters?
Definition
ATP-Binding Cassette transporters; all bind ATP, some act as primary active transporters, some hydrolyze ATP but don't use energy for transport, and in others, ATP binding regulates ion exchange.
Term
Explain the ABC1 subfamily of ABC transporters?
Definition
Involved in transport of phospholipids and cholesterol out of macrophages.
Term
Explain MDR subfamily of ABC transporters?
Definition
Multidrug resistant transporters; primary active transporters that remove cationic drugs and metabolites from cells; found in wide variety of cells; clinically important.
Term
Explain CFTR subfamily of of ABC transporters.
Definition
Cystic fibrosis transmembrane regulator; Cl channel found in apical membrane of many epithelial cells; ATP regulates functioning of this channel.
Term
How does ATP regulate functioning of Cl channel?
Definition
Channel has regulatory domain with site that must be phosphorylated for channel funciton; channel has two nucleotide binding domains to which ATP must bind for channel funciton.
Term
What are tight junctions?
Definition
Very close appositions of adjacent cell membranes; form relatively impermable barriers to movement of substances between cells.
Term
What do tight junctions demarcate?
Definition
The boundary between the apical and basolateral membranes of the epithelial cells.
Term
Where does the apical membrane lie?
Definition
On luminal side of tissue.
Term
Where is the basolateral membrane?
Definition
On the serosal or peritubular side.
Term
Explain how epithelial cells are polarized.
Definition
Complement of transport proteins on apical membrane differs from that on the basolateral membrane; no individual transport protein is found in both membranes; asymmetry allows unidirectional transport of substances across the epithelium.
Term
How are some tight junctions "leaky"?
Definition
Relatively permeant to ions and water; allows for transport of isosmotic solutions.
Term
Give an example of where "leaky" tight junctions are located.
Definition
Small intestine.
Term
Explain impermeant tight junctions.
Definition
They bloc ion diffusion, function to maintain large transepithelial ion or osmotic gradients.
Term
Explain the properties common to most epithelia.
Definition
Na-K pump located on basolateral membrane; most K taken up by Na-K pump leaves cell through K channels in basolateral membrane; Na is lower intracellularly than extracellularly.
Term
Where is the Na-K pump not located on basolateral membrane?
Definition
Choroid plexus.
Term
What are the two pathways for transepithelial transport?
Definition
Transcellular pathway and paracellular pathway.
Term
Explain the transcellular pathway.
Definition
Substances must cross apical membrane, cytoplasm and basolateral membrane of an epithelial cell.
Term
Explain the paracellular pathway.
Definition
Substance moves between epithelial cells through the tight junctions and into the lateral intracellular space.
Term
What is the general mechanism for the transcellular pathway?
Definition
Substance is actively transported in or out on one side of the cell and leaves or enters the other by a passive process (diffusion or facilitated diffusion).
Term
What is the general mechanism for the paracellular pathway?
Definition
Ions or water move through tight junctions between cells in response to electrical or chemical gradients (ions) or osmotic gradients (water).
Term
Explain glucose transport in small intestine.
Definition
Glucose enters cell at luminal border via Na-gradient driven secondary active transport, diffuses across cell cytoplasm; leaves cell at basolateral membrane via facilitated diffusion.
Term
Explain Na absorption.
Definition
Basolateral Na-K pump keeps intracellular Na concentration low, creating a large electrochemical gradient for Na entry; Na channels in apical membrane allow Na to move down gradient into cell; Na that enters is pumped out across basolateral membrane; since Na-K pump creates a net positive charge from lumen to interstitium, Cl moves from lumen to interstitium through paracellular pathway; net result is NaCl absorption in collecting tubule of kidney.
Term
Explain K secretion.
Definition
If apical surface of epithelial cells also contain K channels in addition to Na channels, then some of K that's taken up by Na-K pump can be secreted across apical membrane; mechanism used by the collecting tubule of kidney to secrete it.
Term
What is standing gradient osmosis?
Definition
One of several methods by which epithelial cells transport water and electrolytes.
Term
Where is standing gradient osmosis used?
Definition
By epithelial cells of gall bladder to concentrate bile.
Term
Explain the model of standing gradient osmosis.
Definition
a. Na actively pumped into intercellular spaces.
b. electrical potential created by Na transport draws Cl (and HCO3) into intercellular space.
c. solution in lateral intercellular space becomes hyperosmotic
d. osmotic flow of water occurs into intercellular space from lumen and through surrounding cells.
f. by the time solution reaches serosal border, it's nearly isotonic.
Term
Why is ion diffusion through lipid limited?
Definition
Lipid is non-polar and doesn't accomodate charged particles; lipid bilayer is virtually impermeable to ions.
Term
Most ion channels have what?
Definition
A selectivity filter.
Term
What is a selectivity filter?
Definition
A narrow region of a channel that contains a charged site.
Term
What factors can determine how one ion can be selected over another?
Definition
Size, site strength, and channel configuration.
Term
Most channels exist in what state under resting conditions?
Definition
Closed state.
Term
What are voltage-gated channels?
Definition
A channel in which the probability of opening is increased by voltage change across a membrane.
Term
Give an example of voltage-gated channels.
Definition
Voltage-gated Na channels.
Term
What are ligand-gated ion channels?
Definition
Channels that respond to extracellularly applied chemicals.
Term
Give an example of a ligand-gated ion channel.
Definition
Acetylcholine-receptor channel.
Term
What are messenger-activated channels?
Definition
Channels which respond to intracellular messengers.
Term
Give an example of messenger-activated ion channels.
Definition
ACh activated K channels of heart.
Term
What are stretch-activated channels?
Definition
Channels which open in response to stretch.
Term
Give an example of stretch-activated channels.
Definition
Some sensory receptors.
Term
Explain asymmetry of ion distribution across cell membrane.
Definition
[K]i > [K]o; [Na]i < [Na]o; [Cl]i < [Cl]o; [Ca]i << [Ca]o; [Mg]i = [Mg]o
Term
What role do impermeant, intracellular anions play in the cell?
Definition
They're part of the negative charge in cell interior but don't contribute directly to membrane potential; increase intracellular osmotic pressure.
Term
What are the forces action on ions?
Definition
Chemical gradients and electrical gradients.
Term
What does the Nernst Equation describe?
Definition
The potential across a membrane that will produce an electrical force equal and opposite to the chemical force produced by the difference in concentration of the ion across the membrane; refers to potential inside cell.
Term
What is the Nernst Equation?
Definition
Ex = (RT/ZF)ln([X]o/[X]i); Ex = equilibrium potential for ion X, R = gas constant; T = absolute temperature; ln = natural log; z = valence of ion X; F = Faraday's number; [X]o = external concentration of X, [X]i = internal concentration of X.
Term
What is the Nernst Equation at 37 Celsius and in log10 scale?
Definition
Ex = (60/Z)log10([X]o/[X]i)
Term
What is membrane potential?
Definition
The electrical potential difference between the inside and outside of most cells; also known as resting potential or Em.
Term
Describe the Em inside the cell.
Definition
It's negative and ranges from a few mVs to about -100 mV.
Term
The magnitude of the membrane potential is determined by what?
Definition
The distribution of ions across the membrane and the permeability of the membrane to those ions.
Term
In excitable cells, what ion is most permeable?
Definition
K.
Term
What accounts for deviation of membrane potential from the theoretical value?
Definition
Small permeability to Na.
Term
How is Cl distributed?
Definition
Passively.
Term
How large is the contribution of other ions on Em?
Definition
Negligible.
Term
A steady membrane potential is obtained only when there is what?
Definition
No net ion flux.
Term
Explain how Na and K are out of electrochemical balance.
Definition
Na has large gradient driving it in but small conductance; K has small gradient driving it out but there is high conductance.
Term
Explain how Na and K are out of electrochemical balance.
Definition
Na has large gradient driving it in but small conductance; K has small gradient driving it out but there is high conductance.
Term
How is the ion flux balanced out?
Definition
At rest, efflux of K and influx of Na balance each other out via passive diffusion (or they would if there were no other forces involved).
Term
What is the function of the Na-K ATPase?
Definition
Maintaining the electrical and chemical gradients.
Term
What does the Na-K ATPase do?
Definition
It moves three Na out of cell and two K into cell; creates a membrane potential that's more negative than what would be achieved by passive diffusion; Na-K pump balances gradients out so that there is no net ion flux.
Term
Is the membrane potential in equilibrium?
Definition
No.
Term
What happens during depolarization?
Definition
Em becomes less negative.
Term
What happens during hyperpolarization?
Definition
Em becomes more negative.
Term
Biological membranes act like what?
Definition
Resistors and capacitors in parallel.
Term
Why does it take time for the membrane potential to change in response to an applied current?
Definition
The capacitance of the membrane.
Term
The larger the membrane capacitance, the ________ it will take the potential to reach final level.
Definition
Longer.
Term
What does the time constant describe?
Definition
The time course of the potential change.
Term
What is the time constant for a spherical cell?
Definition
time constant = RmCm = t; where t = time it takes for potential to rise to a value of 1 - 1/e (67%) or fall to a value of 1/e (37%) of its peak value; Rm = resistance of cm2 of membrane; Cm = capacitance of cm2 of membrane.
Term
What happens during graded potentials?
Definition
The amplitude varies with stimulus intensity.
Term
What is electrotonic conduction?
Definition
Decremental conduction; when away from site of stimulus application, response is smaller and slower.
Term
What will determine how final amplitude of a potential varies with distance away from its site of origin?
Definition
Membrane resistance.
Term
What is the length constant?
Definition
The distant at which a potential has fallen to 37% (1/e) of its original value; length constant = square root of rm/ri, where rm = transmembrane resistance per unit length and ri = axial, longitudinal, resistance per unit length of cytoplasm; therefore the larger rm or smaller ri, the longer the length constant.
Term
What is an action potential?
Definition
A large, self-sustaining potential charge; propagated without decrement away from the site of stimulus application.
Term
What is the threshold?
Definition
The value of Em at which a cell produces an action potential.
Term
What is ionic conductance?
Definition
The inverse of resistance.
Term
What affects ionic conductance?
Definition
The higher the resistance, lower the conductance; greater number of channels open, higher the conductance.
Term
How are action potentials possible?
Definition
Voltage-gated channels.
Term
What causes voltage-gated Na channels to open?
Definition
Depolarization.
Term
What causes depolarization?
Definition
Na moves into cell down its electrochemical gradient.
Term
What happens when voltage-gated Na channels inactivate?
Definition
Na entry declines and membrane potential begins to return to resting level.
Term
What opens voltage-gated K channels?
Definition
Depolarization after a slight delay.
Term
What happens when voltage-gated K channels open?
Definition
K leaves cell, leading to repolarization.
Term
At what speed do voltage-gated K channels close?
Definition
Slowly, leading to hyperpolarization thanks to increased K conductance.
Term
Explain threshold.
Definition
The potential at which positive inward current just exceeds the countervailing outward current and thus sets off the positive feedback loop.
Term
What factors effect threshold?
Definition
Density of Na channels, availability of Na channles that can be activated, concentration of divalent cations after threshold (e.g. Ca).
Term
What happens to threshold in hypocalcemia?
Definition
It moves closer to resting membrane potential leading to hyperexcitablility and spontaneous muscle contractions.
Term
What happens to threshold in hypercalcemia?
Definition
It moves further away from resting potential, leading to hypoexcitability and muscle weakness.
Term
What is the refractory period?
Definition
The period of time during or after an action potential in which it is either not possible or its more difficult to generate another action potential.
Term
What happens during the absolute refractory period?
Definition
No matter how strong the stimulus, an additional action potential can be produced, mostly due to Na channel inactivation.
Term
What happens during the relative refractory period?
Definition
Second action potential can be generated but a stronger stimulus is necessary, due to an elevated permeability of K (gK).
Term
What happens during accomodation?
Definition
During a slow depolarization, threshold can be exceed without trigguring action potential; produced by Na channel inactivation and increased gK.
Term
What is the all-or-none response?
Definition
A stimulus either fails to elicit an action potential or it produces on in full-size; doesn't mean that all action potentials are same amplitude.
Term
When do action potentials not have same amplitude?
Definition
Relative refractory period.
Term
What is overshoot?
Definition
Peak potential exceeds - mV, cell polarity is reversed; caused by Em approaching Ena and/or Eca.
Term
Name some variations to normal action potentials.
Definition
Cardiac and smooth muscle action potentials.
Term
Describe cardiac action potentials.
Definition
Initial fast rising phase due in part to fast Na channels; prolonged plateau phase in part to slow, L-type Ca channel; repolarization due to closing slow channels and much delayed reopening of K channels.
Term
Describe smooth muscle action potentials.
Definition
Longer duration than skeletal muscle action potential; rising phase due to slow, L-type Ca channels (sometimes Na channels); repolarization due to closing of slow channels and opening of K channels.
Term
What alters activity of voltage-gated Na channels?
Definition
Neurotoxins and local anesthetic.
Term
What toxins block voltage-gated Na channels?
Definition
Tetrodotoxin (TTX, from puffer fish), saxitoxin (STX, dinoflagellates), u-canotoxin (from marine snail; only blocks Na channels in skeletal muscle).
Term
What local anesthetics block voltage-gated Na channels?
Definition
Cocaine, procaine, lidocain, tetracaine.
Term
How do toxins promote Na channel activity?
Definition
They produce both a longer duration of channel opening and enhanced opening under voltage conditions in which channels are usually closed or inactivated.
Term
What are specific neurotoxins that promote Na channel activity?
Definition
Batrachotoxin (from tropical frogs), veratridine (from plant alkaloids), pyrethrins (from natural plant insecticides), and brevetoxins (from dinoflagellates).
Term
What are the four major types of voltage-gated K channels?
Definition
Delayed outward rectifiers, inward rectifiers, transiet outward rectifiers, and Ca-activated K currents.
Term
Explain delayed outward rectifiers.
Definition
Slow to activate in response to depolarization; allows outward movement of K, inactivates slowly, blocked by tetraethylammonium (TEA).
Term
Explain inward rectifiers.
Definition
Also known as anomalous rectifiers; allow inward movement of K but little outward movement at depolarization; prevent excessive loss of K, blocked by tertiapin.
Term
Explain transient outward rectifiers.
Definition
Activate and inactivate rapidly, activate at more negative channels than other K channels, activated during the afterhyperpolarization phase in some neurons and can control rate of spontaneous action potential discharge; blocked by 4-aminopyridine.
Term
Explain Ca-activated K currents.
Definition
Very common type in various tissues; depolarization on increased intracellular Ca opens them; blocked by Apamin adn Charybdotoxin.
Term
What does conduction velocity depend on?
Definition
Rate of electrotonic current spread down fiber away from active site.
Term
Electrotonic conduction is rate-liming factor in what?
Definition
The speed of propagation of the action potential.
Term
The larger the fiber diameter, the ______ the axial resistance and the _______ the current will spread.
Definition
Lower; farther.
Term
The smaller the capacitance, the ________ the segment of axon will be depolarized, the _______ the current will spread.
Definition
faster; faster.
Term
Conduction velocity is proportional to what?
Definition
length constant/time constant
Term
Explain conduction in muscle of unmyelinated nerves.
Definition
Na entering active region depolarizes adjacent region of plasma membrane, causing region to reach threshold; action potentials are produced in consecutive adjacent regions down nerves or muscle.
Term
What do Schwann cells and oligodendrocytes do?
Definition
Wrap around nerve fibers forming covering (myelin).
Term
Each Schwann cell forms how many segments of myelin on one axon?
Definition
One.
Term
Does each oligodendrocyte form myelin segments on one or many axons?
Definition
Many.
Term
What does myelination do?
Definition
Greatly increases plasma membrane resistance and decreases membrane capacitance.
Term
The increase in membrane resistance leads to what?
Definition
Increased length constant.
Term
What happens due to decreased capacitance?
Definition
Internodal membrane depolarizes more rapidly.
Term
What are the nodes of Ranvier?
Definition
Gaps in myelination.
Term
What is present at the nodes of Ranvier?
Definition
Many Na channels and very few K channels.
Term
What is the internodal region?
Definition
The myelinated portion between nodes.
Term
What is present in the internodal region?
Definition
K channels are localized there, virtually no Na channels.
Term
Action potentials occur where in myelinated nerves?
Definition
Nodes of Ranvier.
Term
What is saltatory conduction?
Definition
The action potentials moving from node to node.
Term
Why are myelinated nerves more energy efficient?
Definition
Transmembrane currents are restricted to small membrane surface area, fewer can traverse membrane and less pumping is necessary to maintain gradients.
Term
Name some demyelination diseases.
Definition
Multiple Sclerosis and Guillain-Barre Syndrome.
Term
What is Multiple Sclerosis.
Definition
Most common demyelination disease of CNS; autoimmune disease; demyelination exposes voltage-gated K channels normally covered, could short circuit action potentials; demyelination also makes K channels accessible to drug therapy.
Term
What is Guillain-Barre Syndrome?
Definition
Most common demyeliniation disease in PNS; demyelination triggered by viral infection; given proper supportive treatment, most patients recover because PNS has ability to remyelinate itself.
Term
What are synapses?
Definition
Specialized places where the information contained in the electrical activity of a nerve is transferred to another cell.
Term
What is the presynaptic element?
Definition
The sending element.
Term
What is the postsynaptic element?
Definition
The receiving element.
Term
What is the synaptic cleft?
Definition
The space between pre- and postsynaptic structures.
Term
What is synaptic delay?
Definition
The time between arrival of an action potential in the presynaptic neuron and a potential change in the postsynaptic cell.
Term
What types of synapses are there?
Definition
Electrical and chemical.
Term
What happens at electrical synapses?
Definition
Communication is by direct passage of current from one cell to another cell.
Term
Describe an electrical synapse.
Definition
Synaptic cleft is small; pre- and postsynaptic elements connected by gap junctions; virtually no synaptic delay; pre- and postsynaptic elements tend to be equal size; transmission is often bidirectional; uncommon in mammals.
Term
What happens at a chemical synapse?
Definition
Communication is via a chemical neurotransmitter.
Term
Describe a chemical synapse.
Definition
Transmitter is contained in vesicles in presynaptic ending; synaptic cleft is large; no electrical connection between pre- and postsynaptic elements; there is a synaptic delay; presynaptic ending often much smaller than postsynaptic cell; postsynaptic cell has neurotransmitter receptors; transmission is unidirectional; most common type of synapse in CNS and PNS.
Term
What is a neuromuscular junction?
Definition
The synapse between a motor neuron and a skeletal muscle fiber; also called myoneural junction or end plate.
Term
Describe the structure of the nmj.
Definition
Presynaptic ending, prominent synaptic cleft, postsynaptic cell.
Term
What is in the presynaptic ending at a neuromuscular junction?
Definition
clear vesicles that contain ACh which accumulate near specialized release sites called active zones which are lined with voltage-gated Ca channels.
Term
Explain the postsynaptic cell at a neuromuscular junction.
Definition
Muscle membrane under presynaptic ending is thrown into a junctional fold with ACh receptors on peaks which are lined up with active zones; acetylcholinesterase found throughout postsynaptic membrane.
Term
Explain the sequence of events during neuromuscular transmission.
Definition
Action potential invades presynaptic ending; depolarization opens voltage-gated Ca channels; Ca influx occurs; Ca causes synaptic vesicles to fuse with the plasma membrane and release ACh via exocytosis; ACh diffuses across synaptic cleft and combines with ACh receptors on postjunctional membrane; opening of monovalent cation channels in postjunctional membrane resulting in depolarization called end plate potential (EPP); muscule membrane surrounding end plate gets depolarized, opening voltage-gated Na channels in muscle membrane and action potential is produced which propagates in both directions away from end plate.
Term
What is the end plate potential?
Definition
Depolarization of the end plate of a neuromuscular junction due to monovalent cation channels being opened.
Term
What has a nearly equal permeability to Na and K?
Definition
ACh channel.
Term
What happens at the ACh channel?
Definition
At resting potential, driving force for Na to enter is greater than driving force for K to leave, creates net influx of Na and consequent depolarization; as muscle fiber depolarizes, driving force for K to leave increases and driving force for Na to enter decreases; at some potential (about half way between equilibrium potential for Na and K, in this case), driving forces for ions is equal, no net current through the ACh channel; this is the equilibrium potential, or reversal potential.
Term
Why is the equilibrium potential also called the reversal potential?
Definition
If the membrane potential exceeds the equilibrium level, the transmitter induced potential reverses polarity (depolarization becomes hyperpolarization).
Term
What is the reversal potential determined by?
Definition
The permeability change it produces.
Term
Give an example of how the permeability change determines the reversal potential for a transmitter.
Definition
If a transmitter increases permeability for only one ion, reversal potential will be at the equilibrium potential of the ion; if transmitter increases permeability of more than one ion, its reversal potential will lie somewhere between the equilibrium potential of the ions involved.
Term
What are miniature end-plate potentials (MEPPS)?
Definition
Small depolarizations that occur at the neuromuscular junction in the absence of nerve stimulation; look and behave like small EPPs.
Term
What is the size of the EPP dependent on?
Definition
The extracellular Ca concentration.
Term
Describe how [Ca]o influences EPPs.
Definition
As [Ca]o is reduced (with increase in Mg to maintain divalent ions) EPP become smaller; a point is reached where size of the EPP can no longer be decreased by reducing [Ca]o - nerve stimulation either produces small potential of nothing at all, smallest evoked EPP is MEPP; size of EPP under condition of low extracellular EPP fluctuates but is always some integral multiple of the size of the MEPP.
Term
How is a MEPP produced?
Definition
By the smallest amount of transmitter.
Term
What are the properties of transmitter release at the neuromuscular junction?
Definition
1. each quantum of transmitter contains thousands of molecules of ACh.
2. normally each action potential releases hundreds of quanta.
3. the amount of transmitter released is far in excess of that necessary to produce an action potential in the muscle.
Term
Where is ACh synthesized?
Definition
The nerve terminal.
Term
What is ACh made by?
Definition
Dietary choline and acetyl CoA.
Term
How is ACh taken up?
Definition
Taken up into vesicles by specific ACh transport proteins in the vesicle membrane.
Term
How is stored ACh released?
Definition
In quantal packets (1 vesicle = 1 quanta).
Term
How many molecules of ACh does each vesicle contain?
Definition
About 10,000.
Term
How many vesicles do presynaptic endings release at a time when done spontaneously?
Definition
Single vesicle.
Term
What results from the spontaneous release of ACh?
Definition
MEPP.
Term
How many vesicles of ACh are released during an action potential?
Definition
Hundreds of vesicles simultaneously.
Term
What results from the vesicle release during an action potential?
Definition
An EPP that is sufficient enough to exceed threshold and trigger an action potential.
Term
What is the action of ACh at the neuromuscular junction stopped by?
Definition
AChE.
Term
What does AChE hydrolyze ACh into?
Definition
acetate and choline.
Term
What is choline taken up by?
Definition
The presynaptic ending to make more ACh.
Term
What is the uptake of choline blocked by?
Definition
Hemicholinium.
Term
What prevents the hydrolysis of ACh, prolonging its action?
Definition
Cholinesterase.
Term
What is myasthenia gravis?
Definition
an autoimmune disorder in which Ab are produced against nicotinic ACh receptors; nerve terminals are normal but ACh receptors at NMJ are sparse and junctional folds are shallow; 2 major forms of disease (one involves only extraocular muscles, other involves all skeletal muscles especially during the day).
Term
What does the drug treatment for myasthenia gravis involve?
Definition
Use of cholinesterase inhibitors.
Term
What is Lambert-Eaton syndrome?
Definition
Patients have Ab against voltage-gated Ca channels in nerve terminals; reduction in Ca influx and consequent reduction in transmitter release; patients exhibit muscular weakness primarily in limb musculature, not ocular muscles.
Term
What percent of patients with Lambert-Eaton syndrome develop or have small cell lung carcinoma?
Definition
50%
Term
Lambert-Eaton can appear up to how many years before lung cancer is diagnosed?
Definition
Three.
Term
What toxins affect the presynaptic action potential?
Definition
Na channel blockers, K channel blockers, and Ca channel blockers
Term
What do Na channel blockers do?
Definition
Prevent action potential and inhibit ACh release.
Term
What are examples of Na channel blockers?
Definition
TTX and STX.
Term
What do K channel blockers do to synaptic transmission?
Definition
Slow repolarization and enhance ACh release by allowing greater Ca influx.
Term
What are some examples of K channel blockers?
Definition
TEA (tetraethylammonium) and dendrotoxin.
Term
What do Ca channel blockers do to synaptic transmission?
Definition
Inhibit Ca influx and thereby inhibit release of ACh.
Term
What are some examples of Ca channel blockers?
Definition
w-canotoxin (maring snail) and some divalent cations (e.g. Co2+).
Term
Name some bacterial toxins that affect synaptic transmission?
Definition
Botulinum toxin and tetanus toxin.
Term
What does the botulinum toxin do to synaptic transmission?
Definition
Inhibit transmitter release from cholinergenic endings (both somatic and autonomic) and enters nerve ending and cleaves proteins related to vesicle fusion and exocytosis.
Term
What does the tetanus toxin do to synaptic transmission?
Definition
Inhibits transmitter release from inhibitory neurons in the spinal cord that normally inhibit muscle contractions by inhibiting alpha motorneurons; toxin enters peripheral nerves and travels to the spinal cord where it eventually ends up in inhibitory interneurons where it exhibits transmitter (glycine) release by cleaving proteins related to vesicle fusion and exocytosis.
Term
Name some agonists of the nicotinic ACh receptor.
Definition
Carbamylcholine and succinylcholine.
Term
What can carbamylcholine or succinylcholine do to synaptic transmission?
Definition
Produce flaccid paralysis; activate ACh receptor and are resistant to hydrolysis of AChE, resulting in prolonged opening of the ACh channels and hence a prolonged depolarization of the muscle; initially there's excitation and tremors followed by relaxation due to inactivatin of voltage-gated Na channels in the muscle membrane because of the prolonged depolarization; ACh receptors eventually desensitize, further inhibiting synaptic transmission.
Term
Name an antagonist of the nicotinic ACh receptor.
Definition
d-Tubocurarine (curare).
Term
What does curare do?
Definition
Causes flaccid paralysis; competitive inhibitor of ACh; binding of curare to ACh receptor doesn't produce depolarization, prevents ACh binding to recepotr, reduces number of receptors available to bind with ACh; inhibition of ACh binding reduces amplitude of EPP to subthreshold levels.
Term
What do inhibitors of AChE do?
Definition
Amplify EPP.
Term
What are some examples of reversible inhibitors of AChE?
Definition
Phystigmine or neostigmine.
Term
What happens with reversible inhibition of AChE?
Definition
prolongs duration and increases amplitude of EPP; agents slowly hydrolyzed and eventually lose effectiveness.
Term
What are some irreversible inhibitors of AChE?
Definition
Organophosphorous compounds.
Term
What happens during irreversible inhibition of AChE?
Definition
Excessive enhancement of cholinergenic transmission; produce death by flaccid paralysis of respiratoyr muscles due to depolarization blockade; made for very lethal nerve gases.
Term
Give an example of an organophosphorous compound.
Definition
Anatoxin (cyanobacteria).
Term
How is muscle classified histologically?
Definition
Striated = cardiac or skeletal
Non-striated = smooth
Term
How is muscle classified in terms of control?
Definition
Voluntary = skeletal
Involuntary = smooth and cardiac.
Term
How is muscle classified in terms of function?
Definition
Skeletal (striated, voluntary): attaches to bones
Smooth (non-striated, involuntary): in hollow organs
Cardiac (striated, involuntary): walls of heart.
Term
Describe the gross anatomy of skeletal muscles.
Definition
-composed of many bundles of elongated, multinucleated cells.
-muscle fibers separated into bundles called fasciculi by connective tissue sheath (perimysium).
-many fasciculi that make up a skeletal muscle are surrounded by a c.t. sheath (epimysium).
Term
Describe the microscopic anatomy of skeletal muscle.
Definition
-membrane surrounding each muscle fiber is the sarcolemma
-each muscle fiber contains hundreds to thousands of myofibrils
-sarcoplasm lies between the myofibril and has mitochondria, several nuclei, and other organelles
-the ER of skeletal muscle is called SR and is very elaborate and highly specialized
-seen with light microscope, skeletal muscle fibers exhibit alternating light bands (I bands) and dark bands (A bands).
Term
What are I bands in skeletal muscle?
Definition
The light bands; regions of thin filaments that are not overlapped with thick filaments.
Term
What are A bands in skeletal muscle?
Definition
The dark band; the thick filaments.
Term
Describe the ultrastructure of skeletal muscle.
Definition
-A dark line (Z line) bisects I band and divides myofibril into sarcomeres.
-thin filaments are attached to Z lines and interdigitate with the thick filaments
- in center of A band is a lighter region, the H band.
- The H band is bisected by a dark band of protein called the M line.
Term
What is the Z line?
Definition
A dark line that determines the border of the sarcomeres.
Term
What is a sarcomere?
Definition
The contractile unit of skeletal muscle and are composed of thick and thin filaments arranged in a precise manner.
Term
What is the H band?
Definition
Has only thick filaments; located in the center of the A band; represents the distance between the ends of the thin filaments.
Term
What is the M line?
Definition
A dark band of protein that links adjacent thick filaments to one another and maintains their alignment.
Term
What are thin filaments made of?
Definition
Actin, tropomyosin, and troponin.
Term
What is actin?
Definition
Molecule that consists of globular proteins (G actin) that polymerize into filamentous double stranded helix (F actin).
Term
What is tropomyosin?
Definition
A thin filamentous protein that lies along the actin molecule and prevents interaction of actin with myosin.
Term
What is troponin?
Definition
A small molecule that acts as a regulatory protein.
Term
What do thick filaments consist of?
Definition
Myosin.
Term
Describe myosin.
Definition
-Each myosin molecule contains two strands which at one end are twisted around each other to form a long tail and at the other form globular heads.
-the aggregation of the tail regions of many myosin molecules forms the thick filament.
-the head regions stick out away from the tails on flexible extensions of the myosin molecule and are called crossbridges.
Term
What other proteins are associated with the myofilaments?
Definition
Nebulin and titin.
Term
What does nebulin do?
Definition
Stretches from Z line to end of each filament; regulates precise length of each thin filament.
Term
What is titin?
Definition
A spring-like protein connecting the Z line to the center of each thick filament.
Term
What are the functions of titin?
Definition
-Maintains the organization and alignment of the thick filaments
-responsible for the passive elastic properties of muscle and allows muscle to recover after being stretched
-may also serve as a mechanoreceptor which participates in mechanical activity-dependent gene regulation and protein degradation.
Term
What do myosin crossbridge contain?
Definition
ATP binding sites.
Term
What can myosin crossbridges act as?
Definition
ATPase.
Term
How is chemical energy transduced into mechanical energy in muscle?
Definition
The interaction of actin and myosin and the consequent splitting of ATP results in the transduction.
Term
What are the steps involved with the chemical to mechanical energy transduction?
Definition
-Ca binds to troponin (leads to conformational change), which results in rotation of tropomyosin molecule which unveils myosin binding sites on the actin.
-Myosin, which in resting state is associated with ADP+Pi, has high affinity for actin and binds to it
-release of P from myosin begins power stroke and crossbridge rotates from 90 degree to 45 degree causing sarcomere to shorten; ADP is released at end of power stroke
-ADP-free myosin complex remains bound to actin until another ATP binds to myosin, which reduces affinity of myosin for actin
-actin and myosin separate and bound ATP is hydrolyzed
-energy from hydrolysis is utilized to re-cock the crossbridge from 45 degree to 90 degree and the crossbridge regains its high affinity for actin
-cycle continues until sarcoplasmic Ca levels return to normal
Term
What happens if muscle becomes depleted of ATP?
Definition
Rigor; myosin stays in attached state
Term
Name the types of contraction skeletal muscle can undergo.
Definition
Isometric and isotonic.
Term
What is isometric contraction?
Definition
Contraction at constant length (no shortening).
Term
What is isotonic contraction?
Definition
Contraction at constant load (shortening).
Term
Do contractions have both isometric and isotonic components?
Definition
Yes.
Term
What can make the isometric portion of contraction longer?
Definition
A heavier load.
Term
Explain the force-length relationship.
Definition
the force produced by a contraction depends on the length of the muscle and is proportional to the amount of overlap of thick and thin filaments in the sarcomeres
-the force needed to stretch a relaxed muscle primarily reflects the elastic properties of the c.t. in muscle and titin.
Term
What does the length-tension curve represent?
Definition
The relationship between muscle length and the amount of tension that a muscle can develop under isometric conditions; also describes the maximum shortening that a contracting muscle can undergo based on the load that it is bearing and the length at which the muscle began to shorten; has relationship with isotonic contraction because with it, muscle length is changing.
Term
What is the velocity of shortening determined by?
Definition
The load; heavier = slower
Term
What does maximum velocity correspond to?
Definition
Maximal cross-bridge cycling rate.
Term
What is the maximum velocity determined by?
Definition
ATPase activity of the myosin present.
Term
What is the sarcoplasmic reticulum?
Definition
An extensive membranous sac structure inside each muscle fiber.
Term
What does the SR consist of?
Definition
Almost entirely of Ca pumps that maintain a low intracellular Ca concentration by actively removing Ca from the sarcoplasm.
Term
What does the inside of SR contain?
Definition
A Ca binding protein called calsequestrin which reduces free Ca in the SR.
Term
What is excitation-contraction coupling?
Definition
The series of events whereby a depolarization leads to interactions between thick and thin filaments.
Term
What does E-C coupling involve?
Definition
Several steps which ultimately alter Ca levels.
Term
What are the steps of E-C coupling?
Definition
-action potential initiated near NMJ travels along surface of muscle and into T-tubules which open to surface
- action potential in T tubules activates a voltage sensor, dihydropyridine (DHP) receptor, located in region of the triad
- DHP receptor undergoes a conformational change during which it interacts mechanically with a protein embedded in SR, the ryanodine receptor, as a result of this mechanical interaction, Ca channels in SR are opened
-Ca leaves SR and binds to tropinin
-this binding produces a conformational change and tropomyosin moves and reveals myosin binding site
-interaction occurs between actin and myosin and fiber contracts
-Ca pumps in SR are activated and Ca concentration is rapidly returned to resting levels producing relaxation.
Term
Explain pathological E-C coupling (Malignant Hyperthermia).
Definition
-autosomal dominant genetic disorder
-affects 1 in 50,000 individuals
-triggered by inhalation anesthetics, particularly halothane, and succinylcholine
-prodced by an abnormality in ryanodine recepotr causing excessive Ca release from SR
-ATP consumption by Ca pumps of SR liberates heat producing the hyperthermia
Term
What are sources of ATP necessary for contraction and relaxation?
Definition
ATP pool, creatine phosphate, anaerobic metabolism (glycolitic), aerobic metabolism (oxidative phosphorylation).
Term
Describe ATP pool.
Definition
While ATP is source of energy for skeletal muscle contraction, ATP pool is small; only enough to support a few seconds o maximal contractile activity.
Term
What is creatine phosphate?
Definition
an immediate high energy source for replenishing ATP; converts ADP to ATP; provides only enough store for energy for less than a minute of maximal activity.
Term
Describe anaerobic metabilism's role with muscle contraction and relaxation.
Definition
Occurs when oxygen supply is inadequate; very rapid production of ATP from glucose or glycogen; inefficient because only 2 moles of ATP/mole glucose; final product of glucose breakdown is lactic acid.
Term
Describe aerobic metabolism.
Definition
occurs when oxygen is readily available; slow process for ATP production; utilizes fatty acids as primary energy source; efficient: 36 moles ATP/mole glucose; final metabolic byproducts are CO2 and H2O.
Term
What is oxygen debt?
Definition
The excess amount of O2 consumed after exercise has ceased; equal to energy consumed minus that supplied by oxidative metabolism.
Term
What is the purpose of the oxygen debt?
Definition
To replenish metabolic stores using aerobic metabolism; creatine phosphate and ATP levels returned to normal; lactic acid either turned back into glucose or glycogen or used to produce ATP.
Term
What types of skeletal muscle fibers are there based on contraction speed and metabolism?
Definition
Slow twitch and fast twitch.
Term
What are slow twitch fibers?
Definition
oxidative or Type I; smallest diameter muscle fibers; contain a myosin which splits ATP at relatively slow rate; highly developed capacity for aerobic metabolism (surrounded by many blood vessels, has myoglobin (red fibers), and contain many mitochondria); low glycogen content; fatigue resistant.
Term
What types of fast twitch fibers are there?
Definition
Type IIb and Type IIa.
Term
Describe Type IIb fibers.
Definition
glycolyticc fibers on the opposite end of the spectrum from Type I; largest diameter; contain myosin which splits ATP at high rate; comparably few mitochondria; no myoglobin; high glycogen stores; fatigable (rely on anaerobic metabolism and quickly exhaust energy stores).
Term
Describe Type IIa fibers.
Definition
oxidative fibers; intermediate between Type I and Type IIb; muscle fibers between Type I and Type IIb; contain myosin which split ATP at high rate but not as high as Type IIb; higher number of mitochondria than Type IIb; contain myoglobin; abundant glycogen stores (more than Type I but less than Type IIb); fatigue resistant and greater capacity for aerobic metabolism than Type IIb.
Term
How are muscles classified as fast or slow twitch muscles?
Definition
Depending on the preponderance of one type of fiber or another.
Term
Classify Latissimus dorsi in terms of what type of muscle it is.
Definition
fast - glycolytic; individual fibers have large diameter; function is rapid movement; low endurance.
Term
Classify vastus lateralis in terms of what type of muscle it is.
Definition
fast - oxidative; moderate diameter fibers; function is moderately rapid movement; moderate endurance.
Term
Classify soleus in terms of what type of muscle it is.
Definition
slow - oxidative; small fiber diameter; function is postural; high endurance.
Term
Classify soleus in terms of what type of muscle it is.
Definition
slow - oxidative; small fiber diameter; function is postural; high endurance.
Term
What is a muscle twitch?
Definition
A mechanical response to a single stimulation.
Term
What is the latent period?
Definition
2-4 ms; the time between stimulus and initiation of contraction.
Term
What happens during the period of contraction?
Definition
-actin and myosin interact
-muscle actively develops tension
-if tension is greater than load resistance have isotonic contraction
-if tension is less than load resistance have isometric contraction.
Term
What happens during the period of relaxation?
Definition
[Ca2+]i returns to normal; tension diminishes.
Term
What does twitch duration depend on?
Definition
Muscle type.
Term
What kind of twitch duration do fast and slow twitch fibers have?
Definition
Fast twitch: short twitch duration
Slow twitch: long twitch duration
Term
What are the factors influencing twitch duration?
Definition
-different rates of ATP hydrolysis by myosin isoforms produce different rates of contraction
-differences in the rate of Ca uptake into SR: activity of Ca pumps in fast twitch fibers is greater than those in slow twitch fibers resulting in quicker Ca uptake and faster relaxation.
Term
What happens due to the duration of a muscle action potential being short compared to twitch duration?
Definition
Muscle can be activated again before it has fully relaxed.
Term
What is summation?
Definition
when a second action potential occurs during relaxation, the force it produces adds to that remaining from the first action potential.
Term
What is tetanus?
Definition
A sustained contraction produced by muscle action potentials occurring repeatedly and rapidly.
Term
What is the tetanic fusion frequency?
Definition
Teh frequency at which the action potentials will occur so rapidly that no relaxation occurs, producing a smooth or fused rise in tension to a plateau; tension is the maximum tension the muscle can produce.
Term
Compare the tension produced during a fused tetanus compared a single twitch.
Definition
Tension produced during plateau of fused tetanus is several times larger than a single twitch; ration varies from 3-8.
Term
What are factors influencing the development of tension?
Definition
Internal Ca concentration, series elastic elements and muscle length.
Term
Explain how internal Ca concentration plays a role in the development of tension.
Definition
-the reuptake of Ca begins as soon as the muscle is stimulated and the elevated Ca concentration is brief compared to development of tension; multiple stimuli are needed to maintain saturating levels of Ca.
Term
What are series elastic elements?
Definition
Structures in a muscle that are stretched when the muscle actively contracts; structures primarily responsible for series elasticity are the crossbridges but tendons also contribute.
Term
What is the effect of the series elastic elements on twitch tension?
Definition
After stimulation, Ca ion release, crossbridge formation and the consequent development of internal tension (active state) occur quickly; much of this tension must be used to stretch the series elastic elements before tension is transmitted to the load; less than full tension is transmitted to load.
Term
What is the effect of tetanus on series elastic elements?
Definition
during a tetanic contraction the repetitive stimuli maintain the internal tension so the series elastic elements remain stretched and more of the internal tension is applied to the load.
Term
How does muscle length influence the development of tension?
Definition
The amount of isometric tension produced by a muscle depends on its initial length; when the situation is such that the thin filaments overlap all the crossbridges, tension development is maximum.
Term
What is a motor unit?
Definition
A motor neuron and all the muscle fibers it innervates.
Term
What happens in large motor units?
Definition
One neuron innervates many muscle fibers and movement is coarse.
Term
What happens in small motor units?
Definition
Only a few fibers are innervated by a single neuron and movement is more delicate.
Term
Are all muscle fibers in a motor unit the same?
Definition
Yes.
Term
What do small motor units contain?
Definition
Slow, oxidative fibers and neurons with small diameter axons.
Term
What do large motor units contain?
Definition
Large diameter axons and fast, glycolytic fibers.
Term
Describe multiple motor unit (spatial) summation.
Definition
Simultaneous activity of motor units influence the degree of contraction; the more motor units that are simultaneously active, the greater the tension produced; small motor units are recruited first.
Term
Describe frequency (temporal) summation.
Definition
the amount of tension developed by an individual motor unit depends on its rate of stimulation; if rate of stimulation is high enough, twitches will sum and at high frequencies, tetanus of the fibers of the motor unit will occur.
Term
What are the general properties of smooth muscle?
Definition
-muscles of hollow organs
-not attached to skeleton
-capable of sustained contractions with a minimum energy expenditure
-innervated by ANS (extrinsic innervation) and by neurons in plexuses within smooth muscle tissue (intrinsic innervation), especially in GI tract.
Term
Describe the histology of smooth muscle fibers.
Definition
-uninucleate
-spindle shaped
-smaller than skeletal muscle fibers
-SR is not as elaborate as skeletal muscle
-no T-tubules but contain rows of caveloae
Term
Explain caveolae.
Definition
-increase surface-to-volume ratio
-often lie close to SR
-contain voltage-gated Ca channels as well as other proteins
-probably involved in many forms of signal transduction.
Term
What types of smooth muscle are there?
Definition
Single unit and multiunit.
Term
Describe single unit (visceral) smooth muscle.
Definition
-most common type
-found in intestines, uterus, small arteries and veins
-cells connected by gap junctions, respond as a unit
-show spontaneous fluctuations in membrane potential that can lead to action potential production and contraction.
Term
What is multiunit smooth muscle.
Definition
-less common
-located in iris and ciliary muscles
-few gap junctions; individual cells respond independently
-allows for finer control
-no spontaneous contractile activity and no action potentials.
Term
Describe contractile proteins.
Definition
-contain myosin, actin, tropomyosin, but no troponin
-not organized into regularly ordered sarcomeres
-thin filament anchor to dense bodies
-each group of thin filaments surround a few thick ones
-more thin than thick filaments compared to skeletal muscle
Term
Explain the biochemistry of activation, contraction and relaxation of smooth muscle.
Definition
-stimulation leads to increase in [Ca]i
-Ca binds to calmodulin
-Ca-calmodulin complex activates myosin light chain kinase (MLCK)
-MLCK phosphorylates light chains of myosin
-phosphorylated myosin interacts with actin, producing contraction
-Ca is actively pumped out of cell or into SR, causing a decrease in [Ca]i
-MLCK inactivates and phosphorylation of myosin stops
-MLC phosphatase dephosphorylates MLC
-smooth muscle relaxes
-contractile force produced by a smooth muscle is thus a balance between phosphorylation and dephosphorylation of myosin light chain.
Term
What happens if myosin is dephosphorylated while attached to actin?
Definition
It detaches slowly; Latch state.
Term
What happens if myosin is not attached to acin when dephosphorylated?
Definition
Myosin loses affinity for actin and does not continue cycling.
Term
What can the contractile force at any given Ca level be modulated by?
Definition
Altering the activity of the kinase and phosphatase.
Term
What does beta 2-receptor activation on vascular or bronchiolar smooth muscle do?
Definition
-increase cAMP levels
-cAMP activates protein kinase A which phosphorylates MLCK
-phosphorylation reduces activity of MLCK resulting in less tension being produced.
Term
What does nitric oxide do?
Definition
-increases intracellular cGMP levels
-cGMP activates protein kinase G which phosphorylates MLCK
-phosphorylation reduces activity of MLCK, resulting in less tension being produed.
Term
What does phospholipase C produce?
Definition
IP3 and diacylglycerol (DAG).
Term
What do IP3 and DAG do in smooth muscle?
Definition
-IP3 induces Ca release from intracellular stores
-DAG activates protein kinase C which phosphorylates MLC phosphatase
-phosphorylation reduces activity of MLC phosphatase resulting in greater tension than would have otherwise been produced.
Term
Explain how Ca influx across the sarcolemma is regulated.
Definition
-voltage-gated Ca channels
-receptor-regulated Ca channels
-store-operated Ca channels.
Term
Describe voltage-gated Ca channels.
Definition
-abundant in smooth muscle cells
-Ca channels opened by dephosphorylation from either slow wave potentials or action potentials.
Term
Describe receptor-regulated Ca channels.
Definition
-channels can be opened by neurotransmitters or hormones
-produce little or no depolarization.
Term
Describe store-operated Ca channels.
Definition
-open when SR levels are low
-replenish SR Ca
Term
What regulates Ca efflux from SR?
Definition
Receptor-regulated efflux and Ca-induced Ca release from SR.
Term
Describe receptor-regulated efflux of Ca from SR.
Definition
-binding of neurotransmitter or hormone to receptor causes formation of a second messenger (IP3) which causes release of Ca from SR
-doesn't involve membrane potential change.
Term
Describe Ca-induced Ca release from SR.
Definition
Ca influx across sarcolemma release Ca from SR
-not as important as Ip3-induced release.
Term
How is extrusion of Ca from myoplasm regulated?
Definition
Sarcolemma pathway and SR pathway.
Term
What does the sarcolemma pathway of Ca extrusion consist of?
Definition
Ca pump and Na-Ca exchanger.
Term
What happens in SR pathway of Ca extrusion?
Definition
-Ca pumps on SR pump Ca into SR
-SR contains Ca-binding proteins calreticulin in addition to calsequestrin.
Term
At what speed does the contraction relaxation cycle in smooth muscle go and why?
Definition
-Slow.
-myosin has very slow attachment and detachment rates
-pumpin of Ca out of myoplasm is slow.
Term
What does crossbridge recycling in smooth muscle require?
Definition
ATP.
Term
Are there any reserves (like creatine phosphate) available in smooth muscle?
Definition
No.
Term
Where does most of the ATP needed for smooth muscle come from?
Definition
Aerobic metabolism.
Term
How can ATP be produced in smooth muscles when O2 levels are low?
Definition
Anaerobic metabolism.
Term
How does the energy requirement for sustained contraction in smooth muscle compare to that in skeletal muscle?
Definition
-much lower
-related to latch state.
Term
Explain the length-tension relationship of smooth muscle.
Definition
Smooth muscles can generate tension under greater stretch than skeletal muscles.
Term
Explain degree of shortening with smooth muscle.
Definition
Smooth muscles can undergo a greater degree of shortening than skeletal muscle.
Term
What is smooth muscle tone?
Definition
A sustained level of tension in a smooth muscle resulting from free Ca.
Term
What is the structure of the neuron-neuron synapse?
Definition
-presynaptic ending
-prominent synaptic cleft
-postsynaptic neuron.
Term
Describe the presynaptic ending.
Definition
-axon expands into a varicosity or a terminal bouton.
-has vesicles contianing neurotransmitter
-presence of electron dense region.
Term
Describe the postsynaptic neuron of neuron-neuron synapses.
Definition
-electron dense region underlies that of presynaptc neuron but membrane not thrown into folds
-contains receptors for neurotransmitters.
Term
What kind of effect can the released transmitter produce on the postsynaptic cell?
Definition
Excitatory or inhibitory.
Term
Explain excitatory transmitter action.
Definition
-conductance change drives membrane potential to a level that is less negative than threshold, results in increase in probability that postsynaptic cell wall produce an action potential
-produces a transient depolarization which is called the Excitatory Postsynaptic Potential (EPSP).
Term
Describe inhibitory transmitter action.
Definition
-conductance change drives membrane potential to a level which is more negative than threshold and thus decreases probability that the postsynaptic cell will produce an action potential
-sometimes produces a transient hyperpolarization known as the Inhibitory Postsynaptic Potential (IPSP)
-important point is that inhibitory transmitters drive membrane potential to a level that is more negative than threshold.
Term
Describe the structure of a neuron.
Definition
Dendrites, cell body, axon.
Term
Describe the dendrites.
Definition
-highly branched processes arising from cell body
-conduct messages toward cell body
Term
Describe cell body (soma).
Definition
-contains nucleus and synthetic machinery.
-axon hillock- place where axon leaves soma.
Term
Describe the axon.
Definition
-single process leaving soma at axon hillock region
-first part of axon is the initial segment
-trigger zone (axon hillock-initial segment region) is where action potentials originate
-carries information away from soma.
Term
Name ways to classify synapses.
Definition
-axodendritic: synapse on dendrite of a neuron
-axosomatic: synapse on soma of neuron
-axoaxonic: synapse on the axon of a neuron.
Term
What are the general considerations of postsynaptic integration of synaptic inputs?
Definition
-since AP are initiated only at trigger zone, AP activity of a neuron is governed by membrane potential at that site alone and that potential in turn is determined by the sum of all synaptic inputs impinging on the neuron at any given time
-because potential change produced by synaptic input is decrementally conducted to trigger zone, inputs closer to this site have greater influence.
Term
Describe spatial summation.
Definition
-arrival of two or more separate inputs at the same time
-inputs either add to one another (e.g. two EPSPs) or subtract from one another (e.g. one EPSP and one IPSP).
Term
Describe temporal summation.
Definition
The build up of synaptic potentials during repetitive stimulation of single input because of the overlap in time of the postsynaptic responses.
Term
What is facilitation?
Definition
-the increase in size of the postsynaptic response during reptitive stimulation of the presynaptic neuron
-lasts less than one second
-results from an increased number of transmitter quanta being released with each succeeding stimulus
Term
What happens at synapse when there is residual Ca left over from preceding action potentials.
Definition
-release of one quantum requires simultaneous bindig of 4 Ca at release sites
-if another AP occurs before all Ca from preceding AP is taken up, new Ca adds to residual Ca causing greater release.
Term
Describe posttetanic potentiation.
Definition
-enhancement of postsynaptic response after subjecting presynaptic neuron to high frequency stimulation for several seconds
-lasts up to several minutes after cessation of stimuli
-due to increased number of transmitter quanta being released per stimulus after the tetanic stimulation
-thought to be due to a saturation of Ca-buffering systems of neuron; excess Ca increases availability of vesicles for release.
Term
Describe long-term potentiation.
Definition
-enhanced transmitter release after a strong tetanic stimulation
-lasts for days or longer
-involves both pre- and postsynaptic events
-serves as a cellular model for memory.
Term
Explain the pre- and postsynaptic events during long-term potentiation.
Definition
-mediated through NMDA receptors on postsynaptic cell
-activation of NMDA receptor leads to production of a retrograde messenger (perhaps NO or CO)
-retrograde messenger diffuses from postsynaptic cell to presynaptic ending, causes an increase in transmitter output from presynapttic ending, probably by acitvating one of more second messenger systems.
Term
Explain depression.
Definition
-decrease in amount of transmitter released after a train of stimuli
-lasts a few sec to a few min depending on duration of stimulation
-occurs at synapses with a high quantal content and is due to depletion of vesicles available for release in presynaptic ending.
Term
Neurotransmitters are substances that:
Definition
-are stored in vesicles at presynaptic ending
-released upon nerve activity
-diffuse to postsynaptic cell and combine with specific receptors
-produce a change in conductance in postsynaptic cell
-inactivation occurs by hydrolysis, uptake, or diffusion.
Term
Name some gaseous transmitters.
Definition
NO and CO.
Term
How do gaseous transmitters behave?
Definition
-nontraditionally
- not stored in vesicles but released when synthesized
-don't combine with surface receptors on postsynaptic cell but rather interact directly with second messenger systems (guanyl cyclase) inside
-inactivation presumably by diffusion away from target.
Term
Name some classic neurotransmitters.
Definition
-acetylcholine
-biogenic amines
-amino acid transmitters
Term
What is acetylcholine?
Definition
-primary transmitter of PNS
-participates in several pathways of CNS
Term
Degeneration of certain cholinergenic paths occurs in what disease?
Definition
Alzheimer's disease.
Term
What are the biogenic amines?
Definition
Catecholamines, serotonin and histamine.
Term
What are catecholamines?
Definition
-synthesized from amino acid, tyrosine
-dopamine, norepinephrine, epinephrine
Term
Where is dopamine found?
Definition
Midbrain and diencephalon.
Term
Degeneration of DA pathways leads to what?
Definition
Parkinsonism.
Term
What group of disorders are linked to DA systems?
Definition
Schizophrenia.
Term
What is norepinephrine?
Definition
Primary transmitter of postganglionic sympathetics.
Term
Where is NE located?
Definition
Widespread NE projections from locus coeruleus in brainsteam to forebrain.
Term
What does NE do?
Definition
Influence sleep, wakefullness, attention and feeding.
Term
Describe epinephrine.
Definition
-established role as hormone in stress response
-recently identified a neurotransmitter in brain of unknown function.
Term
What is serotonin?
Definition
5-hydroxytryptamine, 5-HT; synthesized from tryptophan
-implicated in onset of sleep, mood, emotional behavior, and certain psychotic disorders.
Term
Where is serotonin located?
Definition
Widespread projections from raphe nuclei in brainstem to brain and cerebellum.
Term
What is histamine synthesized from?
Definition
Histidine.
Term
Where is histamine present?
Definition
Mast ccells; in neurons of hypothalamus, which have widespread projections to almost all brain and spinal cord.
Term
What does histamine do?
Definition
Mediate arousal.
Term
What are the amino acid transmitters?
Definition
Glycine, GABA, glutamate, and aspartate.
Term
What is glycine?
Definition
-inhibitory transmitter
Term
Where is glycine found?
Definition
Brainstem and spinal cord.
Term
What is GABA?
Definition
-Gamma-aminobutyric acid.
-important inhibitory transmitter of CNS.
Term
GABA deficit is implicated in what disorder?
Definition
Huntington's chorea.
Term
What are neuropeptides?
Definition
-Polypeptides synthesized de novo in soma packaged in vesicles and transported via axoplasmic transport to axon terminals or sites of release
-some are synthesized as pre-propeptides and are cleaved to form appropriate final product in vesicles
-peptides function as neurotransmitters, neuromodulators and hormones.
Term
How do neuropeptides function as neurotransmitters?
Definition
-released from presynaptic neuron and produce a conductance change in postsynaptic cell
-action terminated by diffusion and also peptidase
Term
How do neuropeptides function as neuromodulators?
Definition
-don't necessarily produce a conductance change in target cell but do alter some aspect of cell function (e.g. excitability, amt of transmitter released, even products synthesized by cells)
-modulatory effects can be slow in onset and slow to dissipate
-all neuromodulators activate G-protein coupled receptors that stimulate an intracellular signal cascade (e.g. activation of adenylyl cyclase and elevation of cAMP).
Term
What are the classes of neuropeptides?
Definition
Opioids, gut0brain and hypophysiotrophic
-many peptides can act as either neuromodulators or transmitters.
Term
What are the opioids?
Definition
Endorphin, enkephalin, dynorphin.
Term
What is endorphin derived from?
Definition
Proopiomelanocortin.
Term
What does endorphins bind to?
Definition
-preferentially to u receptors.
Term
What is enkephalin derived from?
Definition
Proenkephalin.
Term
What does enkephalin bind to?
Definition
Delta receptors.
Term
What is dynorphin derived from?
Definition
Prodynorphin.
Term
What does dynorphin bind to?
Definition
K receptors.
Term
Explain coexistence.
Definition
Many neuropeptides and classical neurotransmitters are found in same nerve terminals.
Term
What are the gaseous transmitters/modulators.
Definition
Nitric oxide, carbon monoxide, hydrogen sulfide.
Term
Explain nitric oxide.
Definition
-first identified as endothelial-derived relaxing factor in blood vessels.
-synthesized from L-arginine by NO synthesis
-not stored in synaptic vesicles but instead diffuses from presynaptic terminal after synthesis
-doesn't bind to receptors on postsynaptic cell but rather diffuses into cell and directly interacts with second messenger systems (e.g. activation of guanylyl cyclase to increase cGMP).
Term
Explain carbon monoxide as a gaseous transmitter/modulator.
Definition
-synthesized from heme by heme oxygenase
-readily diffuses through cell membranes thus released when synthesized
-one major action is activation of guanylyl cyclase.
Term
Describe directly gated ion channels.
Definition
-also known as ligand-gated or ionotropic receptors.
-transmitter receptor is part of ion channel
-types include nicotinic ACh receptor, NMDA glutamate receptor, GABA receptor, glycine receptor.
Term
Explain how the transmitter receptor is a part of the ion channel.
Definition
-single macromolecule forms both the recognition site and ion channel
-binding of neurotransmitter produces a conformational change in macromolecule which results in the opening of the channel.
Term
Describe the nicotinic ACh receptor.
Definition
-binding of two ACh molecules initiates conformational change
-ion channel allows flux of Na into and K out of cell resulting in depolarization.
Term
Describe the NMDA glutamate receptor.
Definition
-behavior is more complex than nicotinic ACh receptor
-cells which contain NMDA receptors usually have non-NMDA glutamate receptors as well; non-NMDA receptor activation depolarizes cell, which when increased, leads to NMDA channels being unplugged and current through channels increases
-Ca entry through NMDA channels results in activation of Ca-dependent 2nd messenger systems (Ca-calmodulin/kinase); too much Ca can result in cell death.
Term
How is the behavior of the NMDA glutamate receptor more complex than that of the nicotinic ACh receptor?
Definition
-ion channel is plugged by Mg at resting potential and doesn't conduct well when activated by glutamate unless membrane is sufficiently depolarized to drive Mg out of cell
-once unplugged, the channel has high permeability to Ca as well as Na and K.
Term
Describe the GABA receptor.
Definition
-receptor is responsible for most of inhibition in CNS
-GABA binding opens Cl selective channel
-in addition to a GABA binding site, the receptor has separate sites that bind other substances which modify GAVA receptor channel activity while having little effects by themselves
-GABA receptor can be modulated by second-messenger pathways.
Term
What substances can bind to GABA receptor and what do they do?
Definition
-benzodiazepines (e.g. Valium): increases frequency of channel opening produced GABA and thus increase Cl current
-barbituates (e.g. Phenobarbital) increase duration of channel opneing produced by GABA and thus increase Cl current
-steroids (e.g. metabolites of testosterone): mimic effects of barbituates
-ethanol: increases GABA-induced Cl current.
Term
What are the second-messenger pathways that modulate the GABA receptor?
Definition
-phosphorylation by either PKC or PKA reduces Cl current
-thus second-messenger pathways can also alter inhibitory activity in CNS.
Term
Describe the glycine receptor.
Definition
-mediates most of the rest of inhibition in CNS not mediated by GABA
-glycine binding opens a Cl selective channel.
Term
Explain receptors that gate ion channels indirectly.
Definition
-receptors linked to G-proteins and constitute the largest group of receptors
-receptor and ion channel are not part of same macromolecule but rather are distinct, separate entities linked together by a G protein
Term
How many pathways are there by which G-proteins modulate ion channels?
Definition
2
Term
Explain the membrane-delimited pathway.
Definition
-G protein directly affects the ion channel
-binding of neurotransmitter to receptor activates G protein and the beta-gamma subunits of the G-protein diffuse through the membrane to interact with nearby channels
-example is M2 ACh receptor on heart which increases K permeability
-the properties include: relatively fast indirect pathway with latency of 30-100 ms; also relatively localized response because of limited diffusion of the G-protein within the membrane.
Term
What is the second pathway of receptors that gate ion channels indirectly?
Definition
-G protein activates a second messenger system
-binding of neurotransmitter to receptor activates G-protein
-G-protein (usually alpha-subunit) activates enzyme which gives rise to 2nd messenger (e.g. Ca, cAMP, cGMP, IP3 and DAG, or arachidonic acid).
Term
What does the secondary messenger do in the second pathway?
Definition
-directly modulates ion channel
0activates a kinase which phosphorylates a protein and this causes the channel to either open or close.
Term
What is an example of a receptor that uses the second pathway?
Definition
The beta 1 receptor activation by NE in heart leads to activation of adenylyl cyclase and increase in cAMP, which activates protein kinase A that phosphorylates L-type Ca channel leading to increase in Ca influx.
Term
What are the properties of the second pathway?
Definition
-slow pathway with a latency of 100s to 1000s ms
-capable of wide spread effects of the production of soluble messengers which can diffuse throughout the cytoplasm
-capable of a great deal of amplification
-can generate very long-lasting changes in cell
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