Ca2+ current-driven nonlinear amplification by the mammalian cochlea in vitro

Ca2+ current-driven nonlinear amplification by the mammalian cochlea in vitro
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DOI:
10.1038/nn1385
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发表时间:
2005-02-01
影响因子:
25
通讯作者:
Hudspeth, AJ
Hudspeth, AJ
中科院分区:
医学1区
文献类型:
--
作者:
Chan, DK;Hudspeth, AJ

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内耳中的活动过程消耗能量以增强听觉的灵敏度和频率选择性。已经提出了两种机制来支持哺乳动物耳蜗中的这一过程:基于受体电位的电运动和Ca2+驱动的主动毛束运动。为了将耳蜗放大器的现象学与这些细胞机制联系起来,我们从长爪沙鼠中开发了一种体外耳蜗制剂,该制剂在模仿其体内环境的同时提供了对感觉上皮的光学访问。声和电刺激引起微音器电位和电诱发的发束运动,表现出完整的正向和反向机械转导。内毛细胞的毛束的机械响应揭示了特征共振和压缩非线性诊断的活动过程。阻断转导与阿米洛利取消非线性放大,而消除所有,但转导电流的Ca2+成分没有。这些结果表明,Ca2+电流驱动的耳蜗活动过程,他们支持的假设,积极的毛束运动的基础耳蜗放大。
An active process in the inner ear expends energy to enhance the sensitivity and frequency selectivity of hearing. Two mechanisms have been proposed to underlie this process in the mammalian cochlea: receptor potential-based electromotility and Ca2+-driven active hair-bundle motility. To link the phenomenology of the cochlear amplifier with these cellular mechanisms, we developed an in vitro cochlear preparation from Meriones unguiculatus that affords optical access to the sensory epithelium while mimicking its in vivo environment. Acoustic and electrical stimulation elicited microphonic potentials and electrically evoked hair-bundle movement, demonstrating intact forward and reverse mechanotransduction. The mechanical responses of hair bundles from inner hair cells revealed a characteristic resonance and a compressive nonlinearity diagnostic of the active process. Blocking transduction with amiloride abolished nonlinear amplification, whereas eliminating all but the Ca2+ component of the transduction current did not. These results suggest that the Ca2+ current drives the cochlear active process, and they support the hypothesis that active hair-bundle motility underlies cochlear amplification.