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Functional contributions of 5 subunit to neuronal acetylcholine receptor channels J. Ramirez-Latorre, C. R. Yu, X. Qu, F. Perin*, A. Karlin† & L. Role‡
Center for Neurobiology and Behavior, Department of Anatomy & Cell Biology, * Ecole Normale Supérieure, † Center for Molecular
Recognition, College of Physicians and Surgeons of Columbia University, P.I. Annex 807, 722 168th Street, New York, New York 10032, USA
‡ To whom correspondence should be addressed
LIGAND-GATED ion channels are multi-subunit complexes where each subunit-type is encoded by several related genes. Hetero-logous expression of any one of the neuronal nicotinic acetylcholine receptors (nAChR) -type subunits, either alone or with any -type subunit, typically yields functional nAChR channels1–5. A striking exception is the nAChR 5 subunit: although apparently complexed with 2 and 4 nAChR subunits in neurons6–8, and expressed in a subset of neurons within the central and peripheral nervous
systems9,10, heterologous expression of 5, either alone or with any P-type subunit has failed to yield functional channels1,11. We demonstrate here that 5 does participate in nAChRs expressed in heterologous systems and in primary neurons, and further that 5 contributes to the lining of functionally unique nAChR channels, but only if coexpressed with both another - and -type subunit. Furthermore, channels containing the 5 subunit are potently activated and desensitized by nanomolar concentrations of nicotine.
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