Stauffer Eric A, Scarborough John D, Hirono Moritoshi, Miller Emilie D, Shah Kavita, Mercer John A, Holt Jeffrey R, Gillespie Peter G
Department of Neuroscience and Department of Otolaryngology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Neuron. 2005 Aug 18;47(4):541-53. doi: 10.1016/j.neuron.2005.07.024.
In sensory hair cells of the inner ear, mechanical amplification of small stimuli requires fast adaptation, the rapid closing of mechanically activated transduction channels. In frog and mouse vestibular hair cells, we found that the rate of fast adaptation depends on both channel opening and stimulus size and that it is modeled well as a release of a mechanical element in series with the transduction apparatus. To determine whether myosin-1c molecules of the adaptation motor are responsible for the release, we introduced the Y61G mutation into the Myo1c locus and generated mice homozygous for this sensitized allele. Measuring transduction and adaptation in the presence of NMB-ADP, an allele-specific inhibitor, we found that the inhibitor not only blocked slow adaptation, as demonstrated previously in transgenic mice, but also inhibited fast adaptation. These results suggest that mechanical activity of myosin-1c is required for fast adaptation in vestibular hair cells.
在内耳的感觉毛细胞中,小刺激的机械放大需要快速适应,即机械激活转导通道的快速关闭。在青蛙和小鼠的前庭毛细胞中,我们发现快速适应的速率取决于通道开放和刺激大小,并且可以很好地模拟为与转导装置串联的机械元件的释放。为了确定适应马达的肌球蛋白-1c分子是否负责这种释放,我们将Y61G突变引入Myo1c基因座并生成了该敏感等位基因的纯合小鼠。在等位基因特异性抑制剂NMB-ADP存在的情况下测量转导和适应,我们发现该抑制剂不仅如先前在转基因小鼠中所证明的那样阻断了缓慢适应,而且还抑制了快速适应。这些结果表明,肌球蛋白-1c的机械活性是前庭毛细胞快速适应所必需的。