The actions of calcium on hair bundle mechanics in mammalian cochlear hair cells
The actions of calcium on hair bundle mechanics in mammalian cochlear hair cells
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DOI：
10.1529/biophysj.107.123257
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Fettiplace, Robert
中科院分区：
文献类型：
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作者：
Beurg, Maryline;Nam, Jong-Hoon;Fettiplace, Robert
声音刺激通过每个毛束的振动来激发耳蜗毛细胞，这打开了机械换能器（MT）通道。我们测量了毛束力学在离体大鼠耳蜗刺激与灵活的玻璃纤维和MT电流的同时记录。内外毛细胞束表现出力-位移关系的非线性，反映了随时间变化的刚度降低。取消的非线性，和发束刚度增加，演习，减少通过MT通道的钙内流：降低细胞外钙，阻断MT电流与双氢链霉素，或去极化为正电位。为了模拟Ca 2+的影响，我们构建了一个有限元模型的外毛细胞束，结合门控弹簧假设MT通道激活。假设四种钙离子与MT通道结合，使其更难打开，此外，Ca 2+被认为会导致通道释放或门控弹簧刚度降低。这两种机制产生的Ca 2+的影响，适应和束力学的实验测量。我们认为，快速适应和力产生的毛束可能源于行动的Ca 2+通道复合物，并不一定需要直接参与的肌球蛋白电机。这些结果的意义耳蜗转导和放大进行了讨论。
Sound stimuli excite cochlear hair cells by vibration of each hair bundle, which opens mechanotransducer (MT) channels. We have measured hair-bundle mechanics in isolated rat cochleas by stimulation with flexible glass fibers and simultaneous recording of the MT current. Both inner and outer hair-cell bundles exhibited force-displacement relationships with a nonlinearity that reflects a time-dependent reduction in stiffness. The nonlinearity was abolished, and hair-bundle stiffness increased, by maneuvers that diminished calcium influx through the MT channels: lowering extracellular calcium, blocking the MT current with dihydrostreptomycin, or depolarizing to positive potentials. To simulate the effects of Ca2+, we constructed a finite-element model of the outer hair cell bundle that incorporates the gating-spring hypothesis for MT channel activation. Four calcium ions were assumed to bind to the MT channel, making it harder to open, and, in addition, Ca2+ was posited to cause either a channel release or a decrease in the gating-spring stiffness. Both mechanisms produced Ca2+ effects on adaptation and bundle mechanics comparable to those measured experimentally. We suggest that fast adaptation and force generation by the hair bundle may stem from the action of Ca2+ on the channel complex and do not necessarily require the direct involvement of a myosin motor. The significance of these results for cochlear transduction and amplification are discussed.