Cl- flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig
Cl- flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig
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DOI：
10.1113/jphysiol.2002.036434
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发表时间：
2003-03-15
影响因子：
5.5
通讯作者：
Santos-Sacchi, J
中科院分区：
文献类型：
--
作者：
Rybalchenko, V;Santos-Sacchi, J
外毛细胞是哺乳动物高频耳蜗放大的基础。快速的体细胞运动可以由马达蛋白普雷斯廷的电压依赖性构象变化驱动，该马达蛋白仅存在于细胞的侧质膜内。然而，尽管细胞有低通膜滤波器，电压驱动的马达如何有助于高频放大仍然是一个谜。最近对普雷斯廷的氯敏感性的鉴定揭示了另一种机制，即普雷斯廷附近的细胞内氯波动可能影响运动。我们报告存在的拉伸敏感的电导内的侧膜，通过阴离子和阳离子，并在声率门控。普雷斯廷附近产生的细胞内Cl-振荡可能驱动马达蛋白转换，如普雷斯廷的状态概率函数沿着电压轴的显著变化所证明的。普雷斯廷的状态概率对细胞内Cl-水平的敏感性预示着Cl-比简单的外部电压传感器更复杂的作用。相反，我们建议由Cl-和其他阴离子的普雷斯廷的变构调制。最后，我们假设，普雷斯廷通过机械激活的侧膜的阴离子通量的敏感性可以提供一个驱动力，绕过膜的低通滤波器，从而允许在高的声学频率放大。
Outer hair cells underlie high frequency cochlear amplification in mammals. Fast somatic motility can be driven by voltage-dependent conformational changes in the motor protein, prestin, which resides exclusively within lateral plasma membrane of the cell. Yet, how a voltage-driven motor could contribute to high frequency amplification, despite the low-pass membrane filter of the cell, remains an enigma. The recent identification of prestin's Cl- sensitivity revealed an alternative mechanism in which intracellular Cl- fluctuations near prestin could influence the motor. We report the existence of a stretch-sensitive conductance within the lateral membrane that passes anions and cations and is gated at acoustic rates. The resultant intracellular Cl- oscillations near prestin may drive motor protein transitions, as evidenced by pronounced shifts in prestin's state-probability function along the voltage axis. The sensitivity of prestin's state probability to intracellular Cl- levels betokens a more complicated role for Cl- than a simple extrinsic voltage sensor. Instead, we suggest an allosteric modulation of prestin by Cl- and other anions. Finally, we hypothesize that prestin sensitivity to anion flux through the mechanically activated lateral membrane can provide a driving force that circumvents the membrane's low-pass filter, thus permitting amplification at high acoustic frequencies.