Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Center for Life Sciences 12251, Boston, MA 02115, USA.
Neuron. 2013 Aug 7;79(3):504-15. doi: 10.1016/j.neuron.2013.06.019. Epub 2013 Jul 18.
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.
听觉和前庭毛细胞中的感觉转导需要跨膜通道样 (Tmc) 1 和 2 基因的表达，但这些基因的功能尚不清楚。为了验证 TMC1 和 TMC2 蛋白是将机械信息转化为电信号的机械敏感离子通道的组成部分的假设，我们记录了表达 Tmc1、Tmc2 或突变 Tmc1 的小鼠毛细胞的全细胞和单通道电流。表达 Tmc2 的细胞具有高钙通透性和大的单通道电流，而表达突变 Tmc1 的细胞钙通透性降低，单通道电流减少。表达 Tmc1 和 Tmc2 的细胞具有广泛的单通道电流，表明 TMC 亚基的多种异源二聚体组装。这些数据表明 TMC1 和 TMC2 是毛细胞转导通道的组成部分，并有助于渗透特性。TMC 通道组成的梯度也可能导致哺乳动物耳蜗音调轴上感觉转导的变化。
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