Stauber NMJ stuff
Terms
- NM transmission can fail by action on ____ and ____.
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Neuron
Post-junctional membrane (muscle)
- Tell me about NM transmission failure by acting on the post-juctional membrane (muscle)
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-Alter ACh binding
-Alter ACh destruction
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How does edrophonium chloride work?
- Block AChE from degrading ACh to choline and acetat, thus prolonging action of ACh
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How does Curare work?
- Bind to ACh receptors and block ACh from binding to open cation channels, thus preventing depolarization
- How can you alter ACh release?
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-Decreased external Ca/increase extracellular Mg: decrease in transmitter output (dec. EPP).
-Botulinum toxin: Most poisonous. Binds irreversibly to presynaptic nerve ending; internalized. Cleaves do
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How does BoTox work?
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Most poisonous.
Binds irreversibly to presynaptic nerve ending; internalized.
Cleaves docking proteins; prevents vesicular release of ACh.
(With time, new nerve endings will grow.)
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Ho do microtubular disrupting agents work?
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They break orientation of microtubules.
Vesicles can't find their way to membrane.
Vesicle contents not released.
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How does alpha-bungarotoxin work?
- Bind to ACh receptors and block ACh from binding to open cation channels, thus preventing depolarization
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How does botulin work?
- Blocks ACh release from vesicles
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How can you regulate ACh receptors?
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-Number of receptors: presence of ACh at EP region directs assembly and insertion of ACh receptors there. [Assembly requires muscle specific tyrosine kinase (MuSK)]
-Myasthenia gravis : autoimmune. An
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How does succinylcholine work?
- Cause cation channels to stay open. (Persistent depolarization results in relaxation)
- Tell me about NM transmission failure by acting on the neuron
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Alteration of ACh synthesis
Alteration of ACh release
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How can you alter ACh synthesis?
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-Analogues of ACh: Hemicholinium blocks uptake of choline by the nerve terminal; limits amount of ACh synth'd
-Metabolic inhibitors: Metabolic poisons block mito function and production of acetyl CoA.
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How does cyanide work?
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Metabolic inhibitor; prevents production of ACh.
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How does hemicholinium work?
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Analogue of ACh
Blocks uptake of choline by nerve terminal
Limits amount of ACh synth'd
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How can you alter ACh binding?
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-Reversible Binding to ACh recptor: Curare. Competitive inhib ACh receptor. Non-depolarizing.
Succinylcholine: High binding affinity for receptors; not hydrolyzed. Depolarizing: opens ion channels, but doesn
- How can you alter ACh destruction?
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Reversible AChE inhibs:Edrophonium (Tensilon) prevents hydrolysis of ACh and enhance marginal NMH function. (Used to diagnose myasthenia gravis)
Irreversible AChE inhibs: Nerve gas inhibit AChE
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How does nerve gas work?
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Suicide inhibitor for AChE. (Irreversible)
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How does DFP (Diisoropylfluorophsphate) work?
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Organophosphate.
Interferes with ACh destruction.
Respiratory paralysis.
- What does myasthenia gravis cause? (In terms of ACh receptors)
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-clustering of receptors
-Internalization and degradation of receptors. (lost)
-Blocking of receptors.
(Weakness and fatigue)
- Weakness comes from ___. (at NMJ)
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-lack of AP innerve
-NMJ failure
-inability to generate MAPs or their spread into muscle
- Ppl w/ myasthenia gravis: what's weakness and fatigue due to?
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Weakness: Non-functional NMJs
Fatigue: Marginal NMJs that fail w/ repeated use