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The Journal of Neuroscience, October 25, 2006, 26(43):10992-11000; doi:10.1523/JNEUROSCI.2188-06.2006

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Cellular/Molecular
A Large-Conductance Calcium-Selective Mechanotransducer Channel in Mammalian Cochlear Hair Cells

Maryline Beurg,¹ Michael G. Evans,² Carole M. Hackney,² and Robert Fettiplace³

¹Equipe Associée 3665 Université Victor Segalen Bordeaux 2, Institut National de la Santé et de la Recherche Médicale, Unité 587, Hôpital Pellegrin, 33076 Bordeaux, France, ²Institute of Science and Technology in Medicine, School of Life Sciences, Keele University, Staffordshire ST5 5BG, United Kingdom, and ³Department of Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53706

Correspondence should be addressed to Robert Fettiplace, 185, Medical Sciences Building, 1300 University Avenue, Madison, WI 53706. Email: fettiplace{at}physiology.wisc.edu

Sound stimuli are detected in the cochlea by opening of hair cell mechanotransducer (MT) channels, one of the few ion channels not yet conclusively identified at a molecular level. To define their performance in situ, we measured MT channel properties in inner hair cells (IHCs) and outer hair cells (OHCs) at two locations in the rat cochlea tuned to different characteristic frequencies (CFs). The conductance (in 0.02 mM calcium) of MT channels from IHCs was estimated as 260 pS at both low-frequency and mid-frequency positions, whereas that from OHCs increased with CFs from 145 to 210 pS. The combination of MT channel conductance and tip link number, assayed from scanning electron micrographs, accounts for variation in whole-cell current amplitude for OHCs and its invariance for IHCs. Channels from apical IHCs and OHCs having a twofold difference in unitary conductance were both highly calcium selective but were distinguishable by a small but significant difference in calcium permeability and in their response to lowering ionic strength. The results imply that the MT channel has properties possessed by few known candidates, and its diversity suggests expression of multiple isoforms.

Key words: auditory; calcium [Ca]; channel; cochlea; hair cell; mechanosensory; transduction

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Received May 23, 2006; revised Sept. 10, 2006; accepted Sept. 11, 2006.

Correspondence should be addressed to Robert Fettiplace, 185, Medical Sciences Building, 1300 University Avenue, Madison, WI 53706. Email: fettiplace{at}physiology.wisc.edu

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