Fast adaptation and Ca2+ sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells.
Fast adaptation and Ca2+ sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells.
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DOI：
10.1523/jneurosci.4566-08.2009
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发表时间：
2009-04-01
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影响因子：
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通讯作者：
Frolenkov GI
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文献类型：
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作者：
Stepanyan R;Frolenkov GI
在内耳毛细胞中，机械转导通道的激活之后是非常快速的失活，这取决于Ca 2+通过这些通道的流入。虽然这种“快速”适应的分子机制在很大程度上是未知的，但主要模型假设Ca 2+敏感性是尚未鉴定的机械转导通道的固有特性。在这里，我们研究了在年轻的出生后shaker 2小鼠（Myo 15 sh 2/sh 2）的毛细胞中的机械转导。这些小鼠没有功能性肌球蛋白-XVa，这对于毛细胞的机械感觉静纤毛的正常生长至关重要。虽然Myo 15 sh 2/sh 2小鼠的内毛细胞和外毛细胞的静纤毛缺乏肌球蛋白-XVa并且异常短，但是这些细胞具有显著不同的毛束形态。Myo 15 sh 2/sh 2外毛细胞保留一个“楼梯”的安排异常短静纤毛和突出的提示链接。Myo 15 sh 2/sh 2内毛细胞没有倾斜取向的尖端链接和他们的mechanosensitivity介导的“顶到顶”的链接之间同样短的静纤毛。在Myo 15 sh 2/sh 2小鼠的内毛细胞和外毛细胞中，我们发现了具有正常“野生型”振幅和激活速度的机械转导反应。令人惊讶的是，只有外毛细胞表现出快速适应和敏感性细胞外Ca 2+。在Myo 15 sh 2/sh 2内毛细胞中，快速适应被破坏，转导电流对细胞外Ca 2+不敏感。我们的结论是Ca 2+敏感性的mechanotransductionchannels和快速适应需要一个结构环境，这是依赖于肌球蛋白-XVa和被破坏的Myo 15 sh 2/sh 2内毛细胞，但不是在Myo 15 sh 2/sh 2外毛细胞。
In inner ear hair cells, activation of mechotransduction channels is followed by extremely rapid deactivation that depends on the influx of Ca2+ through these channels. Although the molecular mechanisms of this “fast” adaptation are largely unknown, the predominant models assume Ca2+ sensitivity as an intrinsic property of yet unidentified mechanotransduction channels. Here we examined mechanotransduction in the hair cells of young postnatal shaker 2 mice (Myo15sh2/sh2). These mice have no functional myosin-XVa, which is critical for normal growth of mechanosensory stereocilia of hair cells. Although stereocilia of both inner and outer hair cells of Myo15sh2/sh2 mice lack myosin-XVa and are abnormally short, these cells have dramatically different hair bundle morphology. Myo15sh2/sh2 outer hair cells retain a “staircase” arrangement of the abnormally short stereocilia and prominent tip links. Myo15sh2/sh2 inner hair cells do not have obliquely oriented tip links and their mechanosensitivity is mediated exclusively by “top-to-top” links between equally short stereocilia. In both inner and outer hair cells of Myo15sh2/sh2 mice, we found mechanotransduction responses with a normal “wild type” amplitude and speed of activation. Surprisingly, only outer hair cells exhibit fast adaptation and sensitivity to extracellular Ca2+. In Myo15sh2/sh2 inner hair cells, fast adaptation is disrupted and the transduction current is insensitive to extracellular Ca2+. We conclude that the Ca2+-sensitivity of the mechanotransduction channels and the fast adaptation require a structural environment that is dependent on myosin-XVa and is disrupted in Myo15sh2/sh2 inner hair cells, but not in Myo15sh2/sh2 outer hair cells.