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Neuromuscular Transmission
UC MED 2015
138
Medical
Graduate
11/18/2011

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Cards

Term
What drug that blocks the gating action of acetylcholine on the acetylcholine channels by competing for the acetylcholine receptor sites?
Definition
curare
Term
What inactivate the acetylcholinesterase in the synapses so that it no longer hydrolyzes acetylcholine?
Definition
neostigmine, physostigmine, and diisopropyl fluorophosphate
Term
What group of drugs can prevent passage of impulses from the nerve ending into the muscle?
Definition
curariform drugs
Term
What compounds have the same effect on a muscle fiber as ACh?
Definition
methacholine, carbachol, and nicotine
Term
What occurs in about 1 in every 20,000 persons, causes muscle paralysis because of inability of the neuromuscular junctions to transmit enough signals from the nerve fibers to the muscle fibers? Pathologically, antibodies that attack the acetylcholine receptors.
Definition
Myasthenia gravis
Term
What allows larger than normal amounts of acetylcholine to accumulate in the synaptic space. Within minutes, some of these paralyzed people can begin to function almost normally?
Definition
neostigmine-used to treat Myasthenia gravis
Term
What blocks the release of synaptic vesicles, abolishes the serotonin release spikes?
Definition
tetanus toxin
Term
What is a short-lived enhancement of the EPP in response to a brief increase in the frequency of nerve stimulation. One way that this may occur is by a transient increase in the mean number of quanta per nerve stimulus
Definition
Facilitation
Term
What is a long-lived and pronounced increase in transmitter release that occurs after a long period of high-frequency nerve stimulation. This effect can last for minutes after the conditioning stimulus. This may be caused by a period of intense nerve firing, which increases [Ca2+]i in the presynaptic terminal and thus increases the probability of exocytosis.
Definition
Potentiation
Term
What are found presynaptically where they are peripherally associated with small synaptic vesicles?
Definition
synapsins
Term
Vesicles are targeted to their release sites by ...
Definition
Rab3A
Term
Synaptic vesicles are sequestered in...
Definition
a storage compartment, as well as a releasable compartment
Term
What entry frees vesicles from the storage compartment through phosphorylation of synapsin?
Definition
calcium
Term
What has this...
-Direct receptor-channel coupling
-Neurotransmitter (NT) binding site and the ion channel are intimately associated in a single macromolecular complex
Definition
Ionotrophic (ligand-gated ion channel) receptor
Term
What has this...

-G protein-mediated receptor channel coupling
--Binding of the neurotransmitter (NT) to its receptor R activates a G protein (G), which then interacts with the ion channel causing it to open
-Second messenger-mediated receptor/channel coupling
Definition
Metabotrophic Receptor
Term
What is needed to activate the nicotinic AChR?
Definition
When 2 molecules of ACh bind to the alpa-subunits exposed to the membrane surface, the receptor channel changes conformation. This opens a pore and both sodium and potassium flow through the open channel
Term
The rings at the external and internal surfaces of the cell membrane may serve as...(this is for the AChR)
Definition
divalent blocking sites
Term
The central ring of the AChR may contribute to the...
Definition
selectively filter for cations
Term
What evoked in a muscle cell normally triggers a postsynaptic action potential and contraction of the muscle?
Definition
EPP
Term
In the absence of nerve stimulation, small depolarizations of 0.5 mV can be recorded, these are called?
Definition
MEPPs
Term
What causes a MEPP?
Definition
spontaneous release of a small amount of ACh
Term
How do EPPs and MEPPS relate?
Definition
EPP is made up of multiple MEPPS
Term
1 MEPP= ______ACh molecules
Definition
5000
Term
Neurotransmitter release would be described as?
Definition
quantal
Term
One quantum represents...
Definition
exocytosis of 1 vesicle and the generation of a MEPP in the postsynaptic muscle cell
Term
What results from 150-200 quanta and is a suprathreshold depolarization?
Definition
EPP
Term
What equals a measure of all muscle fibers?
Definition
CMAP (Compound muscle action potential)
Term
What are the keys of a quantal release at the NMJ (Neuromuscular junction)?
Definition
-150-200 quanta released
-Synaptic potential of about 70 mV
-Suprathreshold
SAFETY FACTOR guarantees the muscle fiber reaches threshold
Term
What are the keys of a quantal release at the CNS synapses?
Definition
-most presynaptic neurons produce postsynaptic (PSP) potentials of 0.5 mV
-Some will be inhibitory
-Multiple simultaneous inputs needed to generate an action potential
Term
What are the symptoms of Myasthenia gravis?
Definition
-Eye muscles; drooping of one or both eyelids (ptosis); double vision (diplopia)
-altered speaking
-difficulty swallowing
-problems chewing
-limited facial expressions
-neck and limb muscles
-respiratory muscles
Term
What disease causes...
-Reduction in number of VGCC
-Highly organized array of channels is disrupted
Definition
Lambert-Eaton Myasthenic Syndrome (LEMS)
Term
Antibodies against the presynaptic voltage-gated calcium channels
Definition
LEMS
Term
Antibodies against the postsynaptic AChR
Definition
Myasthenia gravis
Term
Starts at the extremities and moves up
Definition
LEMS
Term
Starts at the eyes and moves down
Definition
Myasthenia gravis
Term
Weakness improves with activity
Definition
LEMS
Term
Weakness worsens with activity
Definition
Myasthenia gravis
Term
Associated with small cell lung cancer
Definition
LEMS
Term
Associated with thymoma
Definition
Myasthenia gravis
Term
Therapy= aminopyridines
Definition
LEMS
Term
Therapy= ACh esterase inhibitors
Definition
Myasthenia gravis
Term
AChR agonist
Definition
Nicotine
Term
AChE inhibitor
Definition
Physostigmine
Term
Competitive inhibitor of the AChR
Definition
D-tubocurarine
Term
Blocks voltage-gated sodium channels
Definition
Tetrodotoxin and Saxitoxin
Term
Blocks voltage-gated calcium channels
Definition
Conotoxin
Term
Cleaves synaptobrevin
Definition
Tetanus toxin
Term
Cleaves synaptobrevin / syntaxin, SNAP-25
Definition
Botulinum toxin
Term
AChR agonist; Inactivates end-plate sodium channels; Desensitization of the AChR
Definition
Succinylcholine
Term
Irreversible inhibition of AChE
Definition
Organophosphate sompunds
Term
Botox proper name
Definition
Botulinum toxin A (Clostridium botulinum)
Term
Myobloc proper name
Definition
Botulinum toxin B
Term
What drugs does this...
-Weaken nerve to muscle for 4-6 months
-Useful for pts who suffer from abnormal muscle contractions
Definition
Myobloc (Botulinum toxin B)
Term
What are the uses of Clostridial neurotoxins?
Botulinum toxin A (Clostridium botulinum)
Botulinum toxin B
Definition
-Dyastonia
-Cosmetic
-Spasticity following stroke
-Dysphonia
-Hyperhydrosis (blocks nerve to sweat glands)
Term
In Botox what are the purposes of the heavy chain and the light chain?
Definition
heavy chain- facilitates the entry into the synaptic terminal
light chain- protease and cleaves SNAP-25
Term
What is the result of Botox?
Definition
Produces flaccid paralysis by preventing the release of ACh at the neuromuscular junction
Term
Botulinum toxin A & E cleaves?
Definition
SNAP-25
Term
Botulinum toxin C1 cleaves?
Definition
Syntaxin
Term
Botulinum toxin B, D, F, & G cleaves?
Definition
Synatobrevin
Term
What disease...

-Soil spores, animal feces
-Spores germinate and vegetative cells release toxin on lysis
-Toxin passes retrograde along nerve fibers
-Inhibits inhibitory neurons that control the excitability of motor neurons of spinal cord and brainstem
-Trismus (lockjaw) followed by generalized rigidity
-Death by interference with mechanics of respiration
Definition
Clinical Tetanus (Clostridium tetani)
Term
What involves the following...
-Retrograde transport to CNS -30mm/hr
-Inhibits inhibitory glycinergic interneuron
-Hyperexcitation of motor nuerons
-Massive activation of muscle
Definition
Tetanospasmin
Term
What is a highly characteristic, abnormal, sustained spasm of the facial muscles that appears to produce grinning?
Definition
Risus sardonicus
Term
What is a state of a severe hyperextension and spasticity in which an individual's head, neck and spinal column enter into a complete "bridging" or "arching" position.[1] This abnormal posturing is an extrapyramidal effect and is caused by spasm of the axial muscles along the spinal column.
Definition
Ophisthotonus
Term
What is the inability to normally open the mouth due to one of many causes?
Definition
Trismus
Term
Voltage-gated channels open and _______ & __________ ions enter the presynaptic membrane
Definition
sodium and calcium
Term
_________ ions cause __________ ___________ to fuse with the presynaptic membrane
Definition
Calcium
presynaptic vesicles
Term
____________ is liberated into the synaptic cleft.
Definition
ACh
Term
The neurotransmitter reacts with ___________ on the muscle membrane.
Definition
receptors
Term
Channels open and the muscle membrane __________.
Definition
depolarizes
Term
This produces an _______ _________ in the muscle membrane.
Definition
action potential
Term
the neurotransmitter is broken down by ___________ ___________ in the synaptic cleft.
Definition
ACh esterase
Term
___________ is taken up into the presynaptic cell?
Definition
Choline
Term
An isolated nerve-muscle preparation treated with curare would be associated with a decrease in the:
Definition
Amplitude of MEPPs and Amplitude of EPP
Term
What is the difference between an Electrical synapse and Chemical synapse in terms of Distance between pre- and postsynaptic cell membranes?
Definition
Electrical- 3.5 nm
Chemical- 20-40 nm
Term
What is the difference between an Electrical synapse and Chemical synapse in terms of Cytoplasmic continuity between pre- and postsynaptic cells?
Definition
Electrical- Continuity exists
Chemical- Continuity does NOT exist
Term
What is the difference between an Electrical synapse and Chemical synapse in terms of Ultrastructural components?
Definition
Electrical- Gap-junction channels
Chemical- Presynaptic vesicles and active zones; postsynaptic receptors
Term
What is the difference between an Electrical synapse and Chemical synapse in terms of Agent of Transmission
Definition
Electrical- Ion current
Chemical- Chemical transmitter
Term
What is the difference between an Electrical synapse and Chemical synapse in terms of Synaptic delay?
Definition
Electrical- delay is virtually absent
Chemical- Delay is significant: at least 0.3 ms, usually 1-5 ms
Term
What is the difference between an Electrical synapse and Chemical synapse in terms of Direction of Transmission?
Definition
Electrical- Usually bidirectional
Chemical- Unidirectional
Term
What structural function has a role in Glial cell function and disease?
Definition
Gap junctions
Term
Structural function of Gap junctions in glial cells?
Definition
Important for passing small metabolites and ions across the layers of myelin
Term
What disease has these characteristics...
-X-linked
-Deymyelination
-Mutation in connexin32 gene expressed in Schwann cells
Definition
Charcot-Marie Tooth disease
Term
What is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathway?
Definition
Plasticity
Term
What is the method of signal transduction between neurons, which determines whether or not an action potential will be triggered?
Definition
Summation
Term
What are the key points of Metabotropic Receptors?
Definition
-Are not ion channels
-Regulate second messenger cascades
- Exert their action through G proteins
-Enzyme systems associated with these receptors can be either upregulated or downregulated
-A great deal of diversity is possible by pairing different receptors with different effector systems
Term
What residues are phosphorylation sites involved with receptor inactivation in the GPCR?
Definition
serine residues
Term
A G protein-coupled receptor contains how many membrane spanning domains?
Definition
7
Term
What is a type of Metabotropic receptor with subtypes including m1,m3,& m5and m2 & m4.
Definition
Muscarinic acetylcholine receptors
Term
What is the agonist for Muscarinic acetylcholine receptors?
Definition
Muscarine
Term
What has a slower onset and a slower offset? muscarine or nicotine
Definition
muscarine
Term
What is the mechanism the muscarinic acetylcholine receptors m1, m3, and m5?
Definition
-Stimulate PI hydrolysis
-Increase intracellular Ca2+
-Increase cAMP levels
-Release arachidonic acid
-Inhibit M-current (K+)
-Activate Ca2+-dependent K+ and Cl- currents
Term
What is the mechanism the muscarinic acetylcholine receptors m2 and m4?
Definition
-Inhibit adenylyl cyclase
-Stimulate inward-rectified K+ current
-Inhibit Ca2+ currents
Term
A single NT can have both a ______ and _______-term effects on an ion channel.
Definition
short- opens or closes the ion channel for a certain period of time

long-repeated exposure can change gene transcription that can result in an altered ion channel, that is always open or always closed.
Term
What is a consequence of multiple receptors for a neurotransmitter:?
Definition
The activation of different receptors can cause opposite effects on resting membrane potential.
Term
Coactivation of more than one receptor subtype for norepinephrine can result in second-messenger responses, which are...
Definition
1) opposing
2) additive
3) independent
Term
What are the two types of NT Transmission?
Definition
Wired Transmission
and
Volume Transmission
Term
What are the key concepts of Volume Transmission?
Definition
-Release site some distance from target cell
-Neuromodulators
-Range of action limited by diffusion and inactivating enzymes
-Slower onset + longer lasting effects
Term
What can cause cessation of NT action in the CNS?
Definition
-Diffusion
-Reuptake into the synaptic terminal
-Reuptake into glial cells
Term
What is a form of synaptic plasticity which is short-lived and results in increased frequency with no effect on amplitude in the spontaneous postsynaptic potential?
Definition
Post-tetanic Potentiation
Term
What consists of a high-frequency sequence of individual stimulations of a neuron?
Definition
Tetanic stimulation
Term
What is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously? It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. As memories are thought to be encoded by modification of synaptic strength, this is widely considered one of the major cellular mechanisms that underlies learning and memory.
Definition
LTP (Long-Term Potentiation)
Term
Describes the reduction in sensitivity of a synapse's response (excitatory or inhibitory) to incoming signals following a tetanus. This is generally caused by a reduction of the amount of neurotransmitters on hand at the synaptic terminal.
Definition
Post-tetanic depression (Fatigue)
Term
At some synapses depression can last much longer; from minutes to hours, or even several days or months.
Definition
LTD (Long-Term Depression)
Term
What contacts the terminal of a second presynaptic neuron?
Definition
inhibitory neurons or facilitating neurons
Term
Release of neurotransmitter by the inhibitory neuron does what?
Definition
depresses the calcium current, thereby reducing the amount of neurotransmitter released by the presynaptic cell
Term
This results in a depression of the postsynaptic potential (PSP)
Definition
Presynaptic Inhibition
Term
Release of neurotransmitter by the facilitating neuron does what?
Definition
depresses the potassium current in the presynaptic cell, thereby prolonging the action potential and increasing the calcium influx
Term
This results in an increase PSP in the postsynaptic cell
Definition
Presynaptic Facilitation
Term
Tell me the 6 events in Presynaptic Facilitation...
Definition
1) Release of serotonin
2) Increase of cAMP activates protein kinase
3) Activation of a protein that phosphorylates potassium channels
4) These channels usually repolarize the membrane following an action potential
5) Prolonged depolarization results in greater influx of calcium
6) Which lead to greater exocytosis of NT
Result: greater response in motot neuron
Term
What are the general principles of Synaptic Integration?
Definition
-Active inputs contribute proportional to their synaptic strength
-Cell bodies sum inputs and scale nonlinearly
-If above threshold, cell fires
-Cell outputs its activity to other neurons
Term
What are the two resistances in a cable?
Definition
-Membrane resistance-
Increases with: decreasing number of open channels and increasing membrane thickness

-Axial or intracellular resistance
decrease with: increasing cross-sectional area
Term
A more leaky cable has...
Definition
-smaller core diameter
-thinner membrane
-short space constant
-slower conduction
-dendrites
-unmyelinated axons
Term
A less leaky cable has...
Definition
-larger core diameter
-thicker membrane
-longer space constant
-faster conduction
-myelinated axons
Term
What is Fast: mediated by ionotropic receptors that pass sodium and potassium ions?
Definition
EPSPs
Term
What is Fast: mediated by ionotropic GABA and glycine receptors?
Definition
IPSPs
Term
What is associated with NMDA(glutamate receptor) and non-NMDA?
Definition
EPSPs
Term
What has a net inward current results in depolarization of the postsynaptic membrane?
Definition
EPSPs
Term
What has an increased membrane conductance of chloride?
Definition
IPSPs
Term
NT release is _________, so the magnitude of the EPSP is proportional to the amount of NT released.
Definition
quantal
Term
IPSPs can also be induced by...
Definition
metabotropic receptors increasing the permeability to potassium ion leading to hyperpolarization of the postsynaptic membrane
Term
The activation of a receptor can set off a cascade that results in...
Definition
turning on a gene
Term
What synapse is one between the axon of one neuron and the dendrites of another?
Definition
Axodendritic synapse
Term
What synapse is one between the axon of one neuron and the axon of another neuron?
Definition
Axo-axonic synapse
Term
The similarity in the shape of dopamine and _______ permits this drug to function as a dopamine receptor antagonist.
Definition
chlorpromazine
Term
Is this a Therapeutic effect or a Side effect?

Mediated by different types of receptors
Definition
Side effects=TOXIC response
Term
Is this a Therapeutic effect or a Side effect?

Mediated by identical receptors but in different tissues or by different effector pathways
Definition
Therapeutic effect
Term
Is this a Therapeutic effect or a Side effect?

Mediated by same receptor-effector mechanism
Definition
Therapeutic
Term
What is this called...
Drugs can increase rate of synthesis of NT receptors resulting in an increased sensitivity to neurotransmission.
Definition
Up regulation
Term
What is this called...drugs acting at a receptor can affect the number of NT receptors by decreasing the rate of synthesis?
Definition
Down regulation
Term
What is a circuit for spreading stimulation to multiple neurons or neuronal pools?
Definition
Divergence
Term
What is a circuit providing input to a single neuron from multiple sources?
Definition
Convergence
Term
What neurons function in a sequential manner?
Definition
Serial processing
Term
What neuronal circuit has information that is processed simultaneously?
Definition
Parallel processing
Term
What neuronal circuit has a feedback mechanism that may be excitatory or inhibitory?
Definition
Reverberation
Term
What effect will replacing calcium ions in the bathing medium with cobalt ions have on the EPSP and ACh response? Why?
Definition
Replacing calcium ions with cobalt ions in the bathing medium would block the EPSP but not the ACh response.

Calcium entry into the presynaptic terminal through VGCC (which are blocked by cobalt) is necessary for transmitter release and thus an EPSP, but no calcium is necessary for the ACh response.
Term
2. What effect will injection of the presynaptic terminal with botulinum toxin have on the EPSP and the ACh response? Why?
Definition
Injecting the presynaptic terminal with botulinum toxin will block the EPSP because it interferes with the mechanism of release of transmitter vesicles (enzymatic cleaving of the vesicle associated membrane proteins: synaptobrevin / syntaxin, SNAP-25)
Term
What effect will physostigmine to the bathing medium have on the ESPS and the ACh response? Why?
Definition
Physostigmine will augment and prolong the EPSP and the ACh response, because it prolongs the lifetime of acetylcholine at the postsynaptic ACh receptors by blocking enzymatic degration.
Term
What effect will curare to the bathing medium have on the ESPS and the ACh response? Why?
Definition
Curare will block (or at least reduce) both the EPSP and the ACh response, because it will block (or at least partially block) the postsynaptic ACh receptors.
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