Acetylcholine receptor
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2008-06-26T16:41:23Z
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[[Image:ACh.png|thumb|[[Acetylcholine]]]]
An '''acetylcholine receptor''' (abbreviated '''AChR''') is an [[integral membrane protein]] that responds to the binding of the [[neurotransmitter]] [[acetylcholine]].
==Classification==
Like other [[transmembrane receptor]]s, acetylcholine receptors are classified according to their "pharmacology", or according to their relative affinities and sensitivities to different molecules. Although all acetylcholine receptors, by definition, respond to acetylcholine, they respond to other molecules as well.
*[[nicotinic acetylcholine receptor]]s (''nAChR'', also known as "[[ionotropic receptor|ionotropic]]" acetylcholine receptors) are particularly responsive to [[nicotine]]
*[[muscarinic acetylcholine receptor]]s (''mAChR'', also known as "[[metabotropic receptor|metabotropic]]" acetylcholine receptors) are particularly responsive to [[muscarine]].
==Receptor types==
[[Molecular biology]] has shown that the nicotinic and muscarinic receptors belong to distinct protein [[superfamilies]].
===nAChR===
{{Main|Nicotinic acetylcholine receptors}}
The nAChRs are [[ligand]][[ligand-gated ion channel|-gated]] [[ion channel]]s, and, like other members of the "[[cys-loop]]" [[ligand-gated ion channel]] superfamily, are composed of five [[protein subunit]]s symmetrically arranged like staves around a barrel. The subunit composition is highly variable across different tissues. Each subunit contains four regions named M1, M2, M3, and M4, which span the membrane and consist of approximately 20 amino acids. The M2 region, which sits closest to the pore lumen, forms the pore lining.
Binding of acetylcholine to the N termini of each of the two alpha subunits results in the 15° rotation of all M2 helices.<ref name="pmid15165732">{{cite journal | author = Doyle DA | title = Structural changes during ion channel gating | journal = Trends Neurosci. | volume = 27 | issue = 6 | pages = 298–302 | year = 2004 | pmid = 15165732 | doi = 10.1016/j.tins.2004.04.004 }}</ref> The cytoplasm side of the nAChR receptor has rings of high negative charge that determine the specific cation specificity of the receptor and remove the hydration shell often formed by ions in aqueous solution. In the intermediate region of the receptor, within the pore lumen, [[valine]] and [[leucine]] residues (Val 255 and Leu 251) define a hydrophobic region which the dehydrated ion must pass through.<ref name="pmid12827192">{{cite journal | author = Miyazawa A, Fujiyoshi Y, Unwin N | title = Structure and gating mechanism of the acetylcholine receptor pore | journal = Nature | volume = 423 | issue = 6943 | pages = 949–55 | year = 2003 | pmid = 12827192 | doi = 10.1038/nature01748 }}</ref>
nAChR is found at the edges of junctional folds at the [[neuromuscular junction]] on the postsynaptic side, and is activated by acetylcholine release across the synapse. The diffusion of Na<sup>+</sup> and K<sup>+</sup> across the receptor causes depolarization, the end-plate potential, that opens [[voltage-gated sodium channel]]s, which allows for firing of the [[action potential]] and potentially muscular contraction.
===mAChR===
{{Main|Muscarinic acetylcholine receptors}}
In contrast, the [[mAChRs]] are not ion channels, but belong instead to the superfamily of [[G-protein-coupled receptor]]s that activate other ionic channels via a [[second messenger]] cascade.
==Role in health and disease==
Nicotinic acetylcholine receptors can be blocked by [[curare]] and toxins present in the venoms of [[snake]]s and [[shellfish]]es, like [[alpha bungarotoxin|α-bungarotoxin]]. Drugs such as the [[Muscle relaxant|neuromuscular blocking agents]] bind reversibly to the nicotinic receptors in the [[neuromuscular junction]] and are used routinely in anaesthesia.
Nicotinic receptors are the primary mediator of the effects of [[nicotine]]. In [[myasthenia gravis]], the receptor is targeted by [[antibody|antibodies]], leading to muscle weakness.
Muscarinic acetylcholine receptors can be blocked by the drugs [[atropine]] and [[scopolamine]].
==See also==
* [[Muscarinic acetylcholine receptor M5]]
==External links==
* {{MeshName|Acetylcholine+Receptors}}
The muscarine cholinergic receptor activates a G protein when bound to ex.c. ach. The alpha subunit of the Gprotein deactivates adenylate cyclase while the betagamma subunit activates the Kchannels and therefore hyperpolarise the cell. This causes a decrease in cardiac activity.
== References ==
{{Reflist|2}}
{{Ligand-gated ion channels}}
{{G protein-coupled receptors}}
[[Category:Integral membrane proteins]]
[[Category:Molecular neuroscience]]
[[de:Acetylcholinrezeptor]]
[[es:Receptor de acetilcolina]]
[[ja:アセチルコリン受容体]]
[[pl:Receptor acetylocholinowy]]
[[uk:Ацетилхолінові рецептори]]