Editing Acetylcholine receptor (section)

==Role in health and disease==
Nicotinic acetylcholine receptors can be blocked by [[curare]], [[hexamethonium]] and toxins present in the venoms of [[snake]]s and [[shellfish]]es, like [[alpha bungarotoxin|α-bungarotoxin]]. Drugs such as the [[neuromuscular blocking agent]]s 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 [[antibody|antibodies]], leading to muscle weakness.{{cn|date=April 2025}}

Muscarinic acetylcholine receptors can be blocked by the drugs [[atropine]] and [[Hyoscine hydrobromide|scopolamine]].{{cn|date=April 2025}}

[[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.<ref name="Cossins">{{Cite journal
| last1 = Cossins | first1 = J.
| last2 = Burke | first2 = G.
| last3 = Maxwell | first3 = S.
| last4 = Spearman | first4 = H.
| last5 = Man | first5 = S.
| last6 = Kuks | first6 = J.
| last7 = Vincent | first7 = A.
| last8 = Palace | first8 = J.
| last9 = Fuhrer | first9 = C.
| last10 = Beeson | first10 = D.
| title = Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations
| doi = 10.1093/brain/awl219
| journal = Brain
| volume = 129
| issue = 10
| pages = 2773–2783
| year = 2006
| pmid = 16945936
| doi-access = free
}}</ref>

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 with mutations encoding for the [[Alpha5 Nicotinic Acetylcholine Receptor]] cause increased susceptibility to addiction. 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.<ref>{{Cite journal
| last1 = Abicht | first1 = A.
| last2 = Dusl | first2 = M.
| last3 = Gallenmüller | first3 = C.
| last4 = Guergueltcheva | first4 = V.
| last5 = Schara | first5 = U.
| last6 = Della Marina | first6 = A.
| last7 = Wibbeler | first7 = E.
| last8 = Almaras | first8 = S.
| last9 = Mihaylova | first9 = V.
| last10 = Von Der Hagen
| doi = 10.1002/humu.22130 | first10 = M.
| last11 = Huebner | first11 = A.
| last12 = Chaouch | first12 = A.
| last13 = Müller | first13 = J. S.
| last14 = Lochmüller | first14 = H.
| title = Congenital myasthenic syndromes: Achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: A study of 680 patients
| journal = Human Mutation
| volume = 33
| issue = 10
| pages = 1474–1484
| year = 2012
| pmid = 22678886
| s2cid = 30868022
}}</ref> 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.<ref>{{Cite journal
| last1 = Shen | first1 = X. -M.
| last2 = Brengman | first2 = J. M.
| last3 = Edvardson | first3 = S.
| last4 = Sine | first4 = S. M.
| last5 = Engel | first5 = A. G.
| title = Highly fatal fast-channel syndrome caused by AChR subunit mutation at the agonist binding site
| doi = 10.1212/WNL.0b013e31825b5bda
| journal = Neurology
| volume = 79
| issue = 5
| pages = 449–454
| year = 2012
| pmid = 22592360
| pmc =3405251
}}</ref>