The alpha10 nicotinic acetylcholine receptor subunit is required for normal function and development of olivocochlear innervation

DOUGLAS E. VETTER; ELEONORA KATZ; STÉPHANE F. MAISON; JULIÁN TARANDA; SEVIN TURCAN; JIMENA BALLESTERO; M. CHARLES LIBERMAN; A. BELÉN ELGOYHEN; JIM BOULTER

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 2007 vol. 104 p. 20594 - 20599

0027-8424

We report the cloning and characterization of rat a10, a previously unidentified member of the nicotinic acetylcholine receptor (nAChR) subunit gene family. The protein encoded by the a10 nAChR subunit gene is most similar to the rat a9 nAChR, and both a9 and a10 subunit genes are transcribed in adult rat mechanosensory hair cells. Injection of Xenopus laevis oocytes with a10 cRNA alone or in pairwise combinations with either a2-a6 or b2-b4 subunit cRNAs yielded no detectable ACh-gated currents. However, coinjection of a9 and a10 cRNAs resulted in the appearance of an unusual nAChR subtype. Compared with homomeric a9 channels, the a9a10 nAChR subtype displays faster and more extensive agonist-mediated desensitization, a distinct current? voltage relationship, and a biphasic response to changes in extracellular Ca21 ions. The pharmacological profiles of homomeric a9 and heteromeric a9a10 nAChRs are essentially indistinguishable and closely resemble those reported for endogenous cholinergic eceptors found in vertebrate hair cells. Our data suggest that efferent modulation of hair cell function occurs, at least in part, through heteromeric nAChRs assembled from both a9 and a10 subunits.