Ramirez-Latorre J, Yu C R, Qu X, Perin F, Karlin A, Role L
Center for Neurobiology and Behavior, Department of Anatomy and Cell Biology, College of Physicians and Surgeons of Columbia University, New York 10032, USA.
Nature. 1996 Mar 28;380(6572):347-51. doi: 10.1038/380347a0.
Ligand-gated ion channels are multi-subunit complexes where each subunit-type is encoded by several related genes. Heterologous expression of any one of the neuronal nicotinic acetylcholine receptors (nAChR) alpha-type subunits, either alone or with any beta-type subunit, typically yields functional nAChR channels. A striking exception is the nAChR alpha5 subunit: although apparently complexed with beta2 and beta4 nAChR subunits in neurons, and expressed in a subset of neurons within the central and peripheral nervous systems, heterologous expression of alpha5, either alone or with any beta-type subunit has failed to yield functional channels. We demonstrate here that alpha5 does participate in nAChRs expressed in hetrologous systems and in primary neurons, and further that alpha5 contributes to the lining of functionally unique nAChR channels, but only if coexpressed with both another alpha- and beta-type subunit. Furthermore, channels containing the alpha5 subunit are potently activated and desensitized by nanomolar concentrations of nicotine.
配体门控离子通道是多亚基复合物，其中每种亚基类型由几个相关基因编码。任何一种神经元烟碱型乙酰胆碱受体（nAChR）α型亚基单独或与任何β型亚基一起进行异源表达，通常都会产生功能性nAChR通道。一个显著的例外是nAChRα5亚基：尽管它在神经元中显然与β2和β4 nAChR亚基复合，并在中枢和外周神经系统的一部分神经元中表达，但α5单独或与任何β型亚基进行异源表达都未能产生功能性通道。我们在此证明，α5确实参与了在异源系统和原代神经元中表达的nAChR，并且进一步证明，α5有助于形成功能独特的nAChR通道的内衬，但前提是它要与另一种α型和β型亚基共同表达。此外，含有α5亚基的通道会被纳摩尔浓度的尼古丁有效激活并脱敏。
