Biophysics and Development of Cochlear Hair Cells

哺乳动物的耳蜗感受器细胞在形态上和功能上都是二分的。内层 毛细胞(IHC)将听觉信息传递给大脑，而外毛细胞(HC)则放大 机械信号，然后由IHC转换。这两种类型的毛细胞对基底动脉都有反应 通过机械换能器通道产生换能器电流的膜(BM)振动 在立体纤毛的顶端，当它们的发束偏向时。IHCs产生的受体电势 促进神经递质在突触末端的释放。毛细胞产生的感受器电势， 然而，为他们的运动活动提供了输入。毛细胞的躯体运动通常被认为是 负责哺乳动物的耳蜗放大。神经细胞主要由传出神经支配。 纤维起源于脑干。由ACh释放介导的传出作用的影响可以改变 耳蜗区内的微机械事件，从而提供对耳蜗区的“增益控制” 放大器。我们实验室的长期目标是研究毛细胞的运动性、机械性和电性 转导，以及机械放大的机制。具体来说，我们的目标是：1) 研究野生型和prestin突变小鼠毛囊细胞的力学性能；2)研究 电刺激毛细胞受体电流和受体电位的传出激活；3) 研究成人间充质干细胞的力电转导。单独的小鼠OHC将用于AIM 1，而 沙土鼠半壳类制剂将用于目标2和目标3。半壳类制剂将允许 美国将在不同的时间同时测量毛细胞受体电流(或受体电位)和BM运动 机械刺激BM和/或电刺激传出终末时的耳蜗位置 受到刺激。研究毛细胞的机电和机电转导将勾勒出 感觉细胞在听力中的功能。因为大多数患有听力损失的美国人，大约30 数以百万计的人都有某种毛细胞损伤，了解毛细胞的运作是必不可少的 毛细胞相关性听力损失和耳聋的生物修复和预防。

Sensory receptor cells of the mammalian cochlea are morphologically and functionally dichotomized. Inner hair cells (IHCs) transmit auditory information to the brain, while outer hair cells (OHCs) amplify the mechanical signal, which is then transduced by IHCs. Both types of the hair cells respond to basilar membrane (BM) vibration by producing a transducer current through mechanotransducer channels located at the tip of the stereocilia when their hair bundles are deflected. The receptor potential generated by IHCs facilitates the release of neurotransmitters at their synaptic end. The receptor potential produced by OHCs, however, provides the input to their motor activity. Somatic motility of OHCs is generally thought to be responsible for the cochlear amplification in mammals. OHCs are innervated predominantly by efferent fibers originated in the brainstem. The effect of efferent action, mediated by the release of ACh, can alter micromechanical events within the cochlear partition and thereby provides a 'gain control' of the cochlear amplifier. The long-term goal of our laboratory is to study OHC motility, hair cell mechanoelectric transduction, and the mechanisms underlying the mechanical amplification. Specifically, our aims are: 1) to study the mechanical properties of OHCs in wild-type and prestin-mutant mice; 2) to study the effects of efferent activation by electrical stimulation on receptor currents and receptor potentials of the OHCs; 3) to study mechanoelectric transduction of adult IHCs. Isolated mouse OHCs will be used for Aim 1, while gerbil hemicochlea preparations will be used for Aim 2, and Aim 3. The hemicochlea preparation will allow us to measure hair cell receptor currents (or receptor potentials) and BM motion simultaneously at various cochlear locations while the BM is mechanically stimulated and/or the efferent terminals are electrically stimulated. Studying the mechanoelectrical and electromechanical transduction of hair cells will delineate the function of the sensory cells in hearing. Because the majority of Americans with hearing loss, some 30 millions in all,have some kind of hair cell damage, understanding the operation of hair cells is essential to the biological remediation and prevention of hair cell-related hearing loss and deafness.