Stepwise morphological and functional maturation of mechanotransduction in rat outer hair cells
Stepwise morphological and functional maturation of mechanotransduction in rat outer hair cells
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DOI：
10.1523/jneurosci.2159-07.2007
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发表时间：
2007-12-12
影响因子：
5.3
通讯作者：
Ricci, Anthony J.
中科院分区：
文献类型：
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作者：
Waguespack, Jessica;Salles, Felipe T.;Ricci, Anthony J.
内耳机械感觉毛细胞通过精确定位在感觉毛束内的多种蛋白质的协调相互作用，将机械振动转化为电信号。目前的工作确定了在器官型培养中维持的大鼠耳蜗外毛细胞中机电转导（MET）获得和成熟的时间过程。在形态学和功能上观察到一个时空的发育进程，在所有测量特性中，基底耳蜗成熟比顶端耳蜗成熟早2-3天。机械敏感细胞的比例迅速增加，在出生后第0天为基底细胞的中点，并与肌球蛋白IIIa免疫反应性相关。MET电流强度在几天内增加。适应比转导的开始晚一天，成熟得更慢，重叠但先于肌球蛋白i免疫反应性的上升。成熟的适应反应需要不到25%的肌球蛋白Ic表达，这表明该蛋白在毛束功能中具有多种作用。方向性敏感发育迅速，缺乏不成熟的反应，并与径向链的修剪和立体纤毛尖端的增加相关。形态学和电生理学数据支持一种假设，即关键元素独立到达MET位点，随着膜张力的增加，成熟的反应发生，可能是由于尖端连接的张力增加与适应的开始。器官型培养具有正常的、局部特异性的MET反应特性，表明成熟不受外部因素（如神经支配、内淋巴、正常机械刺激或完整的Corti器官）的显著影响。
Inner ear mechanosensory hair cells convert mechanical vibrations into electrical signals via the coordinated interaction of multiple proteins precisely positioned within the sensory hair bundle. Present work identifies the time course for the acquisition and maturation of mechanoelectric transduction (MET) in rat cochlea outer hair cells maintained in organotypic cultures. A spatiotemporal developmental progression was observed morphologically and functionally with basal cochlea maturation preceding apical cochlea by 2-3 d in all measured properties. The fraction of mechanosensitive cells increased rapidly, with a midpoint at postnatal day 0 for basal cells, and correlated with myosin IIIa immunoreactivity. MET current magnitude increased over several days. Adaptation lagged the onset of transduction by a day and matured more slowly, overlapping but preceding the rise in myosin Ic immunoreactivity. Less than similar to 25% of myosin Ic expression was required for the mature adaptation response, suggesting multiple roles for this protein in hair bundle function. Directional sensitivity, lacking in immature responses, developed rapidly and correlated with the pruning of radial links and an increase in tenting of stereociliary tips. Morphological and electrophysiological data support a hypothesis in which key elements arrive independently at the site of MET, with a mature response occurring as membrane tension increases, likely by the increased tensioning of the tip link with the onset of adaptation. Organotypic cultures developed normal, tonotopically specific, MET response properties, suggesting that maturation was not influenced significantly by external factors such as innervation, endolymph, normal mechanical stimulation, or an intact organ of Corti.