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Acetylcholine receptor
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Main page An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the
Contents binding of acetylcholine, a neurotransmitter.
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1 Classification
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2 Receptor types
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2.1 nAChR
Contribute 2.2 mAChR
Help 3 Pharmacology
Community portal 4 Role in health and disease Nicotinic acetylcholine receptor structure
Recent changes 5 See also
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6 References
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Special pages Classification [ edit ]
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Acetylcholine
Like other transmembrane receptors, acetylcholine receptors are classified according to their "pharmacology," or
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according to their relative affinities and sensitivities to different molecules. Although all acetylcholine receptors, by
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definition, respond to acetylcholine, they respond to other molecules as well.

Nicotinic acetylcholine receptors (nAChR, also known as "ionotropic" acetylcholine receptors) are particularly responsive to nicotine. The nicotine ACh
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receptor is also a Na+, K+ and Ca2+ ion channel.
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Muscarinic acetylcholine receptors (mAChR, also known as "metabotropic" acetylcholine receptors) are particularly responsive to muscarine.
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Nicotinic and muscarinic are two main kinds of "cholinergic" receptors.
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Receptor types [ edit ]
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Molecular biology has shown that the nicotinic and muscarinic receptors belong to distinct protein superfamilies. Nicotinic receptors are of two types: Nm and
‫ا‬ Nn. Nm[1] is located in the neuromuscular junction which causes the contraction of skeletal muscles by way of end-plate potential (EPPs). Nn causes
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depolarization in autonomic ganglia resulting in post ganglionic impulse. Nicotinic receptors cause the release of catecholamine from the adrenal medulla, and
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also site specific excitation or inhibition in brain. Both Nm and Nn are Na+ and Ca2+ channel linked but Nn is also linked with an extra K+ channel.
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⽇本語 nAChR [ edit ]

Português Main article: Nicotinic acetylcholine receptor

Русский The nAChRs are ligand-gated ion channels, and, like other members of the "cys-loop" ligand-gated ion channel superfamily, are composed of five protein
中⽂ subunits symmetrically arranged like staves around a barrel. The subunit composition is highly variable across different tissues. Each subunit contains four
15 more regions which span the membrane and consist of approximately 20 amino acids. Region II which sits closest to the pore lumen, forms the pore lining.
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Binding of acetylcholine to the N termini of each of the two alpha subunits results in the 15° rotation of all M2 helices.[2] 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 through which the dehydrated ion must pass.[3]

The nAChR is found at the edges of junctional folds at the neuromuscular junction on the postsynaptic side; it is activated by acetylcholine release across the
synapse. The diffusion of Na+ and K+ across the receptor causes depolarization, the end-plate potential, that opens voltage-gated sodium channels, which
allows for firing of the action potential and potentially muscular contraction.

mAChR [ edit ]
Main article: Muscarinic acetylcholine receptors

In contrast, the mAChRs are not ion channels, but belong instead to the superfamily of G-protein-coupled receptors that activate other ionic channels via a
second messenger cascade. The muscarine cholinergic receptor activates a G-protein when bound to extracellular ACh. The alpha subunit of the G-protein
activates guanylate cyclase (inhibiting the effects of intracellular cAMP) while the beta-gamma subunit activates the K-channels and therefore hyperpolarize the
cell. This causes a decrease in cardiac activity.

Pharmacology [ edit ]

Acetylcholine receptor modulators can be classified by which receptor subtypes they act on:

ACh and its receptors

Drug Nm Nn M1 M2 M3
ACh, Carbachol, Methacholine, AChEi (Physostigmine, Galantamine, Neostigmine, Pyridostigmine) + + + + +
Nicotine, Varenicline + +
Succinylcholine +/-
Atracurium, Vecuronium, Tubocurarine, Pancuronium -
Epibatidine, DMPP +
Trimethaphan, Mecamylamine, Bupropion, Dextromethophan, Hexamethonium -
Muscarine, Oxotremorine, Bethanechol, Pilocarpine + + +
Atropine, Tolterodine, Oxybutynin - - -
Vedaclidine, Talsaclidine, Xanomeline, Ipatropium +
Pirenzepine, Telenzepine -
Methoctramin -
Darifenacin, 4-DAMP, Darifenacin, Solifenacin -

Role in health and disease [ edit ]

Nicotinic acetylcholine receptors can be blocked by curare, hexamethonium and toxins present in the venoms of snakes and shellfishes, like α-bungarotoxin.
Drugs such as the 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 at the neuromuscular junction is targeted by antibodies,
leading to muscle weakness. Muscarinic acetylcholine receptors can be blocked by the drugs atropine and scopolamine.

Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction. Postsynaptic
defects are the most frequent cause of CMS and often result in abnormalities in nicotinic acetylcholine receptors. The majority of mutations causing CMS are
found in the AChR subunits genes.[4]

Out of all mutations associated with CMS, more than half are mutations in one of the four genes encoding the adult acetylcholine receptor subunits. Mutations of
the AChR often result in endplate deficiency. Most of the mutations of the AChR are mutations of the CHRNE gene. The CHRNE gene codes for the epsilon
subunit of the AChR. Most mutations are autosomal recessive loss-of-function mutations and as a result there is endplate AChR deficiency. CHRNE is
associated with changing the kinetic properties of the AChR.[5] One type of mutation of the epsilon subunit of the AChR introduces an Arg into the binding site at
the α/ε subunit interface of the receptor. The addition of a cationic Arg into the anionic environment of the AChR binding site greatly reduces the kinetic
properties of the receptor. The result of the newly introduced ARG is a 30-fold reduction of agonist affinity, 75-fold reduction of gating efficiency, and an
extremely weakened channel opening probability. This type of mutation results in an extremely fatal form of CMS.[6]

See also [ edit ]

Muscarinic acetylcholine receptor M5

Nicotinic agonists

References [ edit ]

1. ^ http://image.slidesharecdn.com/anspharmacologyandcholinergics- 5. ^ Abicht, A.; Dusl, M.; Gallenmüller, C.; Guergueltcheva, V.; Schara, U.; Della
drdhritiupdated2011-111228115516-phpapp02/95/autonomic-nervous-system- Marina, A.; Wibbeler, E.; Almaras, S.; Mihaylova, V.; Von Der Hagen, M.;
pharmacology-and-cholinergics-updated-2011-drdhriti-47-728.jpg? Huebner, A.; Chaouch, A.; Müller, J. S.; Lochmüller, H. (2012). "Congenital
cb=1382965154 myasthenic syndromes: Achievements and limitations of phenotype-guided
2. ^ Doyle DA (2004). "Structural changes during ion channel gating". Trends gene-after-gene sequencing in diagnostic practice: A study of 680 patients".
Neurosci. 27 (6): 298–302. doi:10.1016/j.tins.2004.04.004 . PMID 15165732 . Human Mutation. 33 (10): 1474–1484. doi:10.1002/humu.22130 .
3. ^ Miyazawa A, Fujiyoshi Y, Unwin N (2003). "Structure and gating mechanism of PMID 22678886 .
the acetylcholine receptor pore". Nature. 423 (6943): 949–55. 6. ^ Shen, X. -M.; Brengman, J. M.; Edvardson, S.; Sine, S. M.; Engel, A. G.
doi:10.1038/nature01748 . PMID 12827192 . (2012). "Highly fatal fast-channel syndrome caused by AChR subunit mutation at
4. ^ Cossins, J.; Burke, G.; Maxwell, S.; Spearman, H.; Man, S.; Kuks, J.; Vincent, the agonist binding site" . Neurology. 79 (5): 449–454.
A.; Palace, J.; Fuhrer, C.; Beeson, D. (2006). "Diverse molecular mechanisms doi:10.1212/WNL.0b013e31825b5bda . PMC 3405251 . PMID 22592360 .
involved in AChR deficiency due to rapsyn mutations" . Brain. 129 (10): 2773–
2783. doi:10.1093/brain/awl219 . PMID 16945936 .

External links [ edit ]

Acetylcholine receptor : PMAP The Proteolysis Map-animation Wikimedia Commons has

Acetylcholine+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH) media related to
Acetylcholine receptor.
Acetlycholine Receptor : Molecule of The Month by David Goodsell
Acetylcholine receptors: muscarinic and nicotinic by Flavio Guzman
ANS receptors-overview

V·T·E Ion channel, cell surface receptor: ligand-gated ion channels [show]

V·T·E Cell surface receptor: G protein-coupled receptors [show]

Acetylcholine receptor modulators [show]

Categories: Integral membrane proteins Molecular neuroscience Acetylcholine receptors

This page was last edited on 17 April 2020, at 05:31 (UTC).

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