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Functional contributions of α5 subunit to neuronal acetylcholine receptor channels

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Abstract

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) α-type subunits, either alone or with any β-type subunit, typically yields functional nAChR channels1–5. A striking exception is the nAChR α5 subunit: although apparently complexed with β2 and α4 nAChR subunits in neurons6–8, and expressed in a subset of neurons within the central and peripheral nervous systems9,10, heterologous expression of α5, either alone or with any P-type subunit has failed to yield functional channels1,11. We demonstrate here that α5 does participate in nAChRs expressed in heterologous systems and in primary neurons, and further that α5 contributes to the lining of functionally unique nAChR channels, but only if coexpressed with both another α- and β-type subunit. Furthermore, channels containing the α5 subunit are potently activated and desensitized by nanomolar concentrations of nicotine.

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  1. L. Role: To whom correspondence should be addressed

Authors and Affiliations

  1. Center for Neurobiology and Behavior, Department of Anatomy & Cell Biology, College of Physicians and Surgeons of Columbia University, P.I. Annex 807, 722 168th Street, New York, New York, 10032, USA

    J. Ramirez-Latorre, C. R. Yu, X. Qu & L. Role

  2. Ecole Normale Supérieure, College of Physicians and Surgeons of Columbia University, P.I. Annex 807, 722 168th Street, New York, New York, 10032, USA

    F. Perin

  3. 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

    A. Karlin

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  1. J. Ramirez-Latorre
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  2. C. R. Yu
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  3. X. Qu
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  4. F. Perin
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  5. A. Karlin
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Ramirez-Latorre, J., Yu, C., Qu, X. et al. Functional contributions of α5 subunit to neuronal acetylcholine receptor channels. Nature 380, 347–351 (1996). https://doi.org/10.1038/380347a0

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