Neuronal acetylcholine receptor subunit alpha-4, also known as nAChRα4, is a protein that in humans is encoded by the CHRNA4gene.[5][6] The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAChR). Alpha4-containing nAChRs (specifically the alpha4beta2 subtype) appear to play a crucial role in the addictive response to nicotine.
The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. After binding acetylcholine, these pentameric receptors respond by undergoing an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The protein encoded by this gene is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor.
Mutations in this gene appear to account for a small proportion of the cases of nocturnal frontal lobe epilepsy.[6] It has also been associated with a rare form of movement disorder characterised by dyskinesia during periods of exercise or activity called paroxysmal kinesogenic dyskinesia.[7]
Skorupska E, Rózycka A, Trzeciak WH (2002). "[Molecular and genetic basis of idiopathic nocturnal frontal lobe epilepsy]". Neurol. Neurochir. Pol. 36 (3): 513–25. PMID12185808.
Pilz AJ, Willer E, Povey S, Abbott CM (1993). "The genes coding for phosphoenolpyruvate carboxykinase-1 (PCK1) and neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) map to human chromosome 20, extending the known region of homology with mouse chromosome 2". Ann. Hum. Genet. 56 (Pt 4): 289–93. doi:10.1111/j.1469-1809.1992.tb01155.x. PMID1492743. S2CID23586336.
Steinlein OK, Mulley JC, Propping P, et al. (1995). "A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy". Nat. Genet. 11 (2): 201–3. doi:10.1038/ng1095-201. PMID7550350. S2CID210163.
Phillips HA, Scheffer IE, Berkovic SF, et al. (1995). "Localization of a gene for autosomal dominant nocturnal frontal lobe epilepsy to chromosome 20q 13.2". Nat. Genet. 10 (1): 117–8. doi:10.1038/ng0595-117. PMID7647781. S2CID12912669.
Monteggia LM, Gopalakrishnan M, Touma E, et al. (1995). "Cloning and transient expression of genes encoding the human alpha 4 and beta 2 neuronal nicotinic acetylcholine receptor (nAChR) subunits". Gene. 155 (2): 189–93. doi:10.1016/0378-1119(94)00914-E. PMID7721089.
Elliott KJ, Ellis SB, Berckhan KJ, et al. (1997). "Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits". J. Mol. Neurosci. 7 (3): 217–28. doi:10.1007/BF02736842. PMID8906617. S2CID45737923.
Groot Kormelink PJ, Luyten WH (1997). "Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta3 and beta4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32". FEBS Lett. 400 (3): 309–14. doi:10.1016/S0014-5793(96)01383-X. PMID9009220. S2CID82364119.
Hirose S, Iwata H, Akiyoshi H, et al. (1999). "A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy". Neurology. 53 (8): 1749–53. doi:10.1212/wnl.53.8.1749. PMID10563623. S2CID27745257.
Samochocki M, Zerlin M, Jostock R, et al. (2001). "Galantamine is an allosterically potentiating ligand of the human alpha4/beta2 nAChR". Acta Neurol. Scand. Suppl. 176: 68–73. doi:10.1034/j.1600-0404.2000.00310.x. PMID11261808. S2CID39916984.
Engidawork E, Gulesserian T, Balic N, et al. (2002). "Changes in nicotinic acetylcholine receptor subunits expression in brain of patients with Down syndrome and Alzheimer's disease". In Lubec G (ed.). Protein Expression in Down Syndrome Brain. Journal of Neural Transmission. Supplementum. No. 61. pp. 211–22. doi:10.1007/978-3-7091-6262-0_17. ISBN978-3-211-83704-7. PMID11771745.
