Alpha 10: A determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells

ELGOYHEN AB; VETTER D; KATZ E; ROTHLIN CV; HEINEMANN S; BOULTER J

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

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2001 vol. 98 p. 3501 - 3506

0027-8424

We report the cloning and characterization of rat a10, a previouslyunidentified   member   of   the   nicotinic   acetylcholine   receptor(nAChR) subunit gene family. The protein encoded by the a10nAChR subunit gene is most similar to the rat a9 nAChR, and botha9 and a10 subunit genes are transcribed in adult rat mechanosen-sory hair cells. Injection of Xenopus laevis oocytes with a10 cRNAalone  or  in  pairwise  combinations  with  either a2-a6  or b2-b4subunit cRNAs yielded no detectable ACh-gated currents. How-ever, coinjection of a9 and a10 cRNAs resulted in the appearanceof  an  unusual  nAChR  subtype.  Compared  with  homomeric  a9channels,  the  a9a10  nAChR  subtype  displays  faster  and  moreextensive  agonist-mediated  desensitization,  a  distinct  current?voltage relationship, and a biphasic response to changes in extra-cellular Ca 21 ions. The pharmacological profiles of homomeric a9and heteromeric a9a10 nAChRs are essentially indistinguishableand closely resemble those reported for endogenous cholinergiceceptors found in vertebrate hair cells. Our data suggest that efferentmodulation of hair cell function occurs, at least in part, throughheteromeric nAChRs assembled from both a9 and a10 subunits