Term
Ion transport Poison
-Affect Channels |
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Definition
-Affect the activity of channels in an agonistic way (stimulate flow of ions through channel)/antagonistic way (block ion transport).
-Na
-K
-Ca |
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Term
| Fundamentals of Cell Physiology: Membrane Potential |
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Definition
Cytoplasm/cytosol:
-High concentration of K in the cell (130mmol-140mmol).
-(10mmol-20mmol) of Na in the cell.
Blood Serum/Interstitial fluid:
-High concentration of Na (130mmol to 145mmol) outside cell.
-Low concentration of K () |
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Term
Fundamentals of Cell Physiology: Membrane Potential
-Nernst Potential: Membrane potential in a typical animal cell |
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Definition
(-70mV) normal resting potential of a muscle cell or a nerve cell (when not stimulated)
No pumping in either direction:
-Passive forces into/out of cell
EQUILIBRIUM POTENTIAL FOR THE ION:
-Ion is in equilibrium |
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Term
Fundamentals of Cell Physiology: Membrane Potential
-Nernst Potential: Potassium |
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Definition
(-80mV)
Close to passive distribution in normal animal resting cells |
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Term
Fundamentals of Cell Physiology: Membrane Potential
-Nernst Potential |
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Definition
| The potential at which an ion can be distributed by completely passive forces across a membrane by completely passive transport. |
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Term
Fundamentals of Cell Physiology: Membrane Potential
-Nernst Potential: Sodium |
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Definition
Huge tendency for passive influx of sodium across the plasma membrane into cytoplasm. If Na is to be removed from living cell, Na needs to be pumped out actively at the expense of ATP.
-Why: Have a negatively charged membrane potential (-70mV) the the sodium distribution across the membrane in an animal cell under normal conditions is such that in the surrounding medium (interstitial fluid) the concentration of Na is 135mmol to 145mmol.
-Not as salty as the ocean (500mmol).
-Na in blood serum and interstitial fluid. |
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Term
Fundamentals of Cell Physiology: Membrane Potential
-Concentration of K in the blood serum and interstitial fluid |
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Definition
3.5mmol-5.5mmol outside cell
-very little potassium in the interstitial fluid/blood serum. |
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Term
Fundamentals of Cell Physiology: Membrane Potential
-Concentration of Na in the cytoplasm, cytosol |
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Definition
| Typically no more than 10mmol-20mmol of sodium in a normal cell (cytosol) when not stimulated by an action potential, when at rest. |
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Term
| Outside cell: Blood Serum/Interstitial Fluid |
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Definition
| Very little K (3.5mmol-5.5mmol) and lots of Na (135mmol-145mmol) |
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Term
| Inside Cell: Cytoplasm/Cytosol |
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Definition
| Little Na (10mmol-20mmol) lots of K (100mmol-140mmol) |
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Term
Ion transport Poison
-Affect ATPases |
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Definition
Affect the hyrdolysis of ATP molecules
-Poisons affect transporters
ATP->ADP + NPi + (dG=30-50kJ/mol):
-Energy used to transport ions. |
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Term
Ion transport Poison
-Transport Poisons |
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Definition
Doesn't affect channels or ATPase:
-affects transport/transmission of nerve signals, nerve to muscle stimuli profoundly
-disruptions neurotransmitter transport and binding |
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Term
Fundamentals:
Toxicants vs. Neurotransmitter Poisons. |
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Definition
| Toxicants that affect ions channels or ATPases act is fundamentally the same as the way neurotransmitter poisons act |
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Term
Fundamentals:
Membrane Polarizations |
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Definition
Mircoelectrodes measure potentials:
-12:00 Lecture 6 |
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Term
Fundamentals:
Master enzyme in animal cells across living membranes |
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Definition
Sodium-Potassium ATPase:
-Sodium ATPase and Potassium ATPase coupled together transport two ions simultaneously in opposite directions.
- 3 Na ions eflux (out), 2 K ions influx (in).
-Sodium can flow into cell passively
-normally sodium has to be transported out.
-Potassium flows passively out
-Normally Potassium needs to be transported out.
-Pumps both Sodium/Potassium against concentration and electrochemical potential.
-consumes the largest amount of energy by far (50% of all usable energy).
-Makes disequilibrium possible. |
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Term
| Foxglove (Digitalis purpurea) |
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Definition
-Toxin (made by biological entity)
-Has two glycosides: digoxin, digitoxin. |
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Term
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Definition
Affect the sodium/potassium ATPase in the heart muscle cells:
-myocites of the heart
-cells are less able to distribute NA/K properly
-membrane potential much less negative (drift toward positive)
-cells become less excitable, and become paralyzed.
-collapsed electrochemical gradient across the plasma membrane
Results in cellular paralysis when Sodium/Potassium ATPases are knocked out.
Digitoxin, digoxin:
-chemically similar
-block ATPase
Although target is heart muscles, if available in large concentrations in blood, it will affect other parts of the body as well. |
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Term
Time line of Paralysis:
When Na/K ATPases are blocked |
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Definition
Paralyze electrically then functionally:
-Individual cells, entire tissues and then entire organisms. |
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Term
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Definition
Commonly encountered toxicological symptom:
-Snake bite/organic pollutants (excessive amounts): paralyze parts of body
Minamata Disease:
-Organic mercury poisoning
-Paralysis: First in limbs and then progressively throughout the entire body. |
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Term
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Definition
-Electrochemical gradient across plasma membrane collapsed
-No electric transfer from one nerve to another, thus no movement of muscle
-Can't move into action potential, because ion distribution pumps poisoned. |
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Term
Types of Paralysis
-Flaccid
-Spastic (Tetanic) |
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Definition
Flaccid: No movement, limp, -electrochemical gradients collapsed
-paraplegics, quadriplegics.
Spastic: spasm, tense, no movement
Over stimulation
-Tetanus |
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Term
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Definition
Levels of Expression:
-local: finger, leg, arm
-Entire organism: spasm or flaccidity. |
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Term
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Definition
| Type of paralysis that can come about with both faccidity and spasticity. |
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Term
| How to get either flaccidity or spasticity both locally and globally |
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Definition
| Act on ion channels or ATPases or Neurotransmittors. |
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Term
| Partial Paralysis can lead to full paralysis and perhaps death |
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Definition
Flaccidity: limbs are simply hanging a little
-sleep paralysis: atonic state during REM sleep in subject is paralyzed for several minutes when awake. (temporary)
Spastic: stomach spasms, if paralysis where to continue could affect vital organs. |
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Term
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Definition
| The tendency of ions to diffuse through open channels, counteracted by Na/K Enzyme |
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Term
Flaccid/Spastic Paralysis
Na Channel |
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Definition
Na channels: how action potentials are generated within nerve cell:
-signal travels down the axon to the terminal nerve cell
-transferance of a signal from nerve cell to effector organ (muscle)
Either way need to open up Na channels:
-The reason that humans and think and move is because have learned to use vast electrochemical gradient from the inside of the cell to the outside. |
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Term
Flaccid/Spastic Paralysis
Open Na Channel |
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Definition
When open, Na rushed from the interstitial fluid into the cytosol:
-Quick (mSeconds)
-turns the membrane potential from (-70mV) to (+60mV) (action potential) |
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Term
Flaccid/Spastic Paralysis
Multimeric Protein |
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Definition
Sodium Channels (and most potassium channels) are multimeric proteins:
-tetrameric channel assembly: made of 4 subunits that must coassemble to give functional integral ion channel
-each subunit is different from one another, but each sub unit comes from the same gene.
-only when all four are assembled can a pore be created for the ion to pass through.
Modifications that hang on to the subunits are post-transcriptional modifications:
-ATP binding sites, phosphorylation sites, accessory proteins change the conformation of each subunit |
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Term
Flaccid/Spastic Paralysis
-parts of a Na channel |
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Definition
Voltage Sensor
Cell Activity Filter (ion selectivity):
-Oxygens that ressemble O in H2O that would normally surround Na in aqueous solution.
-replicates O arm length of Na in solution
-when Na approached channel, it is stripped of hydration shell.
-arm length allows channel to distinguish between ions(have different arm lengths).
Various Binding Sites on Subunits (can bind to toxicants/toxins) |
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Term
Flaccid/Spastic Paralysis
-Tetrodotoxin |
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Definition
| Pufferfish poison, newts, widespread. Made by bacteria (Vibrio) that live in associate with animal |
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