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18 Cards in this Set
- Front
- Back
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What type of synapse is the neuromuscular junction?
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A chemical synapse
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What is the active zone?
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The presynaptic storage and release site for vesicles
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What is the motor endplate?
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sarcolemma opposite synaptic terminals that has receptors for ACh
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Where is the highest concentration of ACh receptors?
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junctional (synaptic) folds
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What is the sarcolemma?
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-the plasma membrane of a muscle fiber
-electrically similar to axonal plasma membranes -can propagate self-regenerating action potentials -action potentials due to voltage-gated channels |
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What is the motor end plate?
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-the sarcolemma that is immediately adjacent to the synaptic terminal
-can be depolarized -ion channels are chemically gated -capable of End Plate Potentials (EPP) |
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What type of receptors are the neuromuscular acetylcholine receptors?
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nicotinic acetylcholine receptors
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How does the channel open to Na+ and K+?
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- alpha subunits must bind ACh (one each) for the channel to open
-the binding of one ACh facilitates the binding of another -the frequency of channel opening is dependent on ACh concentration |
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How do EPPs come about?
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- Each vesicle release of ACh causes a miniature end-plate potential (MEPP)
-the summation of multiple MEPPs produce an EPP -Graded potential EPP is confined to the MEP |
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What is the margin of safety?
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- the difference between the size of the EPP and the size of the threshold stimulus needed to evoke an AP
-typically far more ACh released and receptors activated than needed for depolarization -provides a buffer to prevent catastrophic failure of neuromuscular transmission |
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How is ACh recycled?
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-rapidly degraded by Acetylcholinesterase
-choline recycled and synthesized from acetyl-coA |
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What are the steps in Neuromuscular Transmission?
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1. AP in the alpha motor neuron
2.Ca+2 through voltage-gated channels 3.ACh vesicle migration and fusion 4. ACh release into the synaptic cleft 5. binding of ACh to the ACh receptor and Na+ influx 6. EPP 7. if threshold is reached then opening of voltage-gated Na+ channels and depolarization of the sarcolemma 8. Degradation of acetylcholine by acetylcholinesterase (AChE) |
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What do non-depolariziong neuromuscular blocking drugs do?
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-majority of clinically-relevant blockers
-competitively block binding of ACh to receptors causing paralysis -reversible -TUBOCURARINE (curare)= competitive antagonist against ACh used during surgery as an adjunct to but not as a replacement for anethesia |
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How do depolarizing neuromuscular blocking drugs work?
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-depolarize the sarcolemma of the muscle fiber
-prevents further activation of the muscle -SUCCINYLCHOLINE= used to induce muscle relaxation and short term paralysis; usually to make endotracheal intubation possible -mimics the effect of ACh but degrades much slower |
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What is the Botulism Toxin?
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-anaerobic organism sometimes found in improperly canned food
-wound botulism= rare complication of trauma or heroin use -the toxin is taken up during vesicle recycling - the toxin then degrades synaptobrevin, SNAP-25 or syntaxin -prevents fusion of synaptic vesicles -target= NMJ and cholinergic nerve endings in ANS -results in flaccid paralysis and death via respiratory paralysis -ex= botox |
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What occurs with Anticholinesterase poisoning?
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-inhibits acetylchoinesterase
-ACh accumulates in the synaptic cleft and its action is prolonged -depolarizing muscle block -initially causes muscle fasciculations followed by muscle weakness -weakness due to receptor desensitization and a possible conformational change in the receptor -found in pesticides and nerve gases |
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What is Myasthenia Gravis
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-autoimmune neuromuscular disease characterized by muscle weakness
-circulating antibodies block ACh receptors on the postsynaptic junction -EPP decreases -decreased margin of safety -recruitment declines with use; some motor units fail to reach threshold due to decreased margin of safety -treated with cholinesterase inhibitors |
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What is a reversible acetylcholinesterase inhibitor?
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-NEOSTIGMINE= prolongs and enhances action of ACh at motor end plate
-used to improve muscle tone in people with myasthenia gravis (reduced number of ACh receptors) -used in anesthesia at the end of an operation to reverse the effects of non-depolarizing muscle relaxants |
