TMC1 and TMC2 Are Components of the Mechanotransduction Channel in Hair Cells of the Mammalian Inner Ear

被引:317
作者
Pan, Bifeng [1 ]
Geleoc, Gwenaelle S. [1 ]
Asai, Yukako [1 ]
Horwitz, Geoffrey C. [1 ]
Kurima, Kiyoto [2 ]
Ishikawa, Kotaro [2 ]
Kawashima, Yoshiyuki [2 ]
Griffith, Andrew J. [2 ]
Holt, Jeffrey R. [1 ]
机构
[1] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Otolaryngol,FM Kirby Neurobiol Ctr, Boston, MA 02115 USA
[2] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD 20850 USA
关键词
MECHANOELECTRICAL TRANSDUCER CHANNELS; MECHANOSENSITIVE CHANNELS; FUNCTIONAL MATURATION; SENSORY TRANSDUCTION; MOUSE COCHLEA; C; ELEGANS; ADAPTATION; CALCIUM; DOMINANT; DEAFNESS;
D O I
10.1016/j.neuron.2013.06.019
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Sensory transduction in auditory and vestibular hair cells requires expression of transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into electrical signals, we recorded whole-cell and single-channel currents from mouse hair cells that expressed Tmc1, Tmc2, or mutant Tmc1. Cells that expressed Tmc2 had high calcium permeability and large single-channel currents, while cells with mutant Tmc1 had reduced calcium permeability and reduced single-channel currents. Cells that expressed Tmc1 and Tmc2 had a broad range of single-channel currents, suggesting multiple heteromeric assemblies of TMC subunits. The data demonstrate TMC1 and TMC2 are components of hair cell transduction channels and contribute to permeation properties. Gradients in TMC channel composition may also contribute to variation in sensory transduction along the tonotopic axis of the mammalian cochlea.
引用
收藏
页码:504 / 515
页数:12
相关论文
共 41 条
[1]   Production and characterization of improved adenovirus vectors with the E1, E2b, and E3 genes deleted [J].
Amalfitano, A ;
Hauser, MA ;
Hu, HM ;
Serra, D ;
Begy, CR ;
Chamberlain, JS .
JOURNAL OF VIROLOGY, 1998, 72 (02) :926-933
[2]   Eukaryotic Mechanosensitive Channels [J].
Arnadottir, Johanna ;
Chalfie, Martin .
ANNUAL REVIEW OF BIOPHYSICS, VOL 39, 2010, 39 :111-137
[3]  
ASSAD JA, 1992, J NEUROSCI, V12, P3291
[4]   A large-conductance calcium-selective mechanotransducer channel in mammalian cochlear hair cells [J].
Beurg, Maryline ;
Evans, Michael G. ;
Hackney, Carole M. ;
Fettiplace, Robert .
JOURNAL OF NEUROSCIENCE, 2006, 26 (43) :10992-11000
[5]   Localization of inner hair cell mechanotransducer channels using high-speed calcium imaging [J].
Beurg, Maryline ;
Fettiplace, Robert ;
Nam, Jong-Hoon ;
Ricci, Anthony J. .
NATURE NEUROSCIENCE, 2009, 12 (05) :553-558
[6]   tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans [J].
Chatzigeorgiou, Marios ;
Bang, Sangsu ;
Hwang, Sun Wook ;
Schafer, William R. .
NATURE, 2013, 494 (7435) :95-99
[7]   TRP channels in mechanosensation: direct or indirect activation? [J].
Christensen, Adam P. ;
Corey, David P. .
NATURE REVIEWS NEUROSCIENCE, 2007, 8 (07) :510-521
[8]  
COREY DP, 1983, J NEUROSCI, V3, P962
[9]   THE ACTIONS OF CALCIUM ON THE MECHANOELECTRICAL TRANSDUCER CURRENT OF TURTLE HAIR-CELLS [J].
CRAWFORD, AC ;
EVANS, MG ;
FETTIPLACE, R .
JOURNAL OF PHYSIOLOGY-LONDON, 1991, 434 :369-398
[10]   Calcium imaging of single stereocilia in hair cells: Localization of transduction channels at both ends of tip links [J].
Denk, W ;
Holt, JR ;
Shepherd, GMG ;
Corey, DP .
NEURON, 1995, 15 (06) :1311-1321