Cholinergic (ACh) Receptors

[liveonearth]

--two types: nicotinic and muscarinic
--transmembrane proteins



NICOTINIC
--aka nAChR, "ionotropic" acetylcholine receptors
--stimulated by nicotene
--in autonomic ganglia; sympathetic AND parasympathetic!
--in adrenal medulla
--in neuromuscular junction receptors are different from autonomic ones
--signal transduced via ligand-gated non-selective cation channels
--antagonists: hexamethonium (ganglionic) and tubocuranine (motor endplates)
--composed of five protein subunits symmetrically arranged like staves around a barrel
--subunit composition highly variable by tissue
--ea subunit contains four regions which span the membrane, approx 20 amino acids
--region II forms the pore lining
--found at the neuromuscular junction on the postsynaptic side
--activated by acetylcholine release across the synapse
--diffusion of Na+ and K+ across the receptor causes depolarization
-->opens voltage gated Na+ channels-->action potential fires-->muscle contracts
--can be blocked by curare, snake venom, shellfish toxins, ex: α-bungarotoxin
--drugs that bind reversibly to nicotinic receptors at the NMJ routinely in anaesthesia
--PATHOL: receptor targeted by autoantibodies in myasthenia gravis-->muscle weakness

NICOTINIC AGONISTS


MUSCARINIC
--aka mAChR, "metabotropic" acetylcholine receptors
--stimulated by muscarine
--postsynaptic parasympathetic
--sweat glands, salivation
--signal transduced via second messenger, NOT ionic channel
--receptor subtypes use different second messengers:
--M1 & 2-->PLC-->IP3, DAG
--M3 & 4-->inhibit andenylate cyclase-->decrease cAMP
--antagonist: atropine, scopolamine


NOTES ON SECOND MESSENGERS
--PLC = phospholipase C
--PLC cleaves phosphatidylinositol 4,5-biphosphate (PIP2)
-->increase in inositol triphosphate (IP3) and diacylglycerol (DAG)
--IP3 binds & activates InsP3 receptor on membrane of endoplasmic/sarcoplasmic reticuli
-->opens calcium channel-->Ca2+ released into cyto/sarcoplasm-->activates another Ca2+ channel-->more Ca2+
--in smooth muscle increased Ca2+ causes contraction

HEART EFFECTS


OVERVIEW


NOTE TO SELF
last quarter in a lab dx post I covered cholinesterase inhibitors (pesticides)


EFFECTS OF SMOKING