The mammalian cochlea relies on active electromotility of outer hair cells (OHCs) to resolve sound frequencies. OHCs use ionic channels and somatic electromotility to achieve the process. It is unclear, though, how the kinetics of voltage-gated ionic channels operate to overcome extrinsic viscous drag on OHCs at high frequency. Here, we report ultrafast electromechanical gating of clustered Kv7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-Kv7.4 were revealed, using optogenetics strategies. Upon clustering, the half-activation voltage shifted negative, and the speed of activation increased relative to solitary channels. Clustering also rendered Kv7.4 channels mechanically sensitive, confirmed in consolidated Kv7.4 channels at the base of OHCs. Kv7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast Kv7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies.

中文翻译：

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Kv7.4 通道的协同性赋予耳蜗外毛细胞超快的机电灵敏度和紧急特性。

哺乳动物耳蜗依靠外毛细胞 (OHC) 的主动电动性来解析声音频率。OHC 使用离子通道和体细胞电动性来实现该过程。然而，目前尚不清楚电压门控离子通道的动力学如何运作以克服高频下对 OHC 的外在粘性阻力。在这里，我们报告了 OHC 中集群 Kv7.4 的超快机电门控。使用光遗传学策略揭示了由聚集 Kv7.4 之间的协同性引起的动力学和灵敏度的增加。聚集后，半激活电压向负移动，激活速度相对于孤立通道增加。聚类还使 Kv7.4 通道具有机械敏感性，这在 OHC 底部的合并 Kv7.4 通道中得到证实。Kv7. 4 个簇为 OHC 提供超快机电通道门控，其大小和速度沿耳蜗轴变化。超快 Kv7.4 门控为 OHC 提供了一种反馈机制，使耳蜗能够克服粘性阻力并解决听觉频率的声音。