Term
| What are the major anatomical sites of cholinergic neurotransmission? |
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Definition
1) Skeletal NMJ- voluntary contraction
2) CNS- cognition, emotion and motor control
3) Autonomic PNS- regulation of heart, blood vessels, gland and visceral organs |
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Term
| What are the major events of Neurotransmission at cholinergic synapses? |
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Definition
1) Uptake of choline by sodium-dependent transporter (RLS)
2) Choline acetyl transferase makes ACh from acetyl CoA and Choline
3) ACh is packaged into vesicle and those vesicles exhibit stimulation-dependent and calcium-dependent fusion and release at the synapse
4) Binds to nAChR or mAChR and removed from synapse by AChE |
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Term
| What are the 2 major types of NMJ blockers and why are they used? |
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Definition
NMJ blockers are used intravenously during anesthesia and surgery.
1) Depolarizing (Succinylcholine- reversible)
- bind nAChR and induce opening of ion channel. They are not degraded by AChE, so it leads to initial fascultations and then flaccid paralysis.
2) Competitive (Curare. d-tubocurarine, pancuronium, mivacurium)
- Antagonists of AChe, competing for binding site at nAChR. Only need to bind 1 out of 2 binding sites to prevent ion channel opening! |
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Term
| How does a BOTOX injection work? |
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Definition
| Cleaves presynaptic SNAP-25, inhibiting vesicle fusion and ACh exocytosis (lasts weeks to months). |
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Term
| How does neuronal AChRs differ from those at the NMJ? |
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Definition
Neuronal only express alpha and beta subunits (example is a4/b2 in the brain).
BOTH pre-synaptically and post-synaptically. |
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Term
| What are the effects of nicotine stimulation on AChRs? |
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Definition
Requires B2 subunits for reinforcing/addictive properties, such as those seen in peripheral ganglia.
Activation of nACh receptors by nicotine stimulates release of dopamine and glutamine as well!. |
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Term
| What is the course of events following mAChR binding? |
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Definition
| GPCR mechanisms, where cAMP and IP3 act on ion channels |
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Term
| Where are mAChRs found and what compounds inhibit their action? |
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Definition
1) Five subtypes found in PNS on autonomic effector cells in ganglia and endothelial cells of blood vessels
- In CNS, found in hippocampus, cortex and thalamus.
2) Inhibited non-selectively by atropine and scopolamine (Like NMJ blockers, mAChR inhibitors are used as anesthetic pre-medications, as well as COPD, PD, mushroom toxicity and incontinence) |
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Term
| What drugs inhibit AChE and how are they used clinically? |
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Definition
2) Drugs cause ACh to accumulate in synapse and are used in patients with myasthenia gravis (autoantibodies against nAChR), glaucoma and AD (controversial)
**Irreversible agents such as organophosphates and sarin gas are TOXIC. Give the peripheral antidote quickly!** |
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Term
| Explain the most likely cause of Gulf war syndrome. |
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Definition
| Soldiers were given somewhat reversible anti-AChE drugs like Pyridostigmine as prophylaxis against irreversible cholinesterase inhibitor poisoning (sarin can and organophosphates) |
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