Biophysics and Development of Cochlear Hair Cells

描述（由申请人提供）：哺乳动物耳蜗的感觉受体细胞在形态和功能上是二分的。内毛细胞（IHC）将听觉信息传递到大脑，而外毛细胞（OHC）放大机械信号，然后由IHC进行转导。这两种类型的毛细胞响应基底膜（BM）的振动，产生一个传感器电流通过位于静纤毛的尖端mechanotransducer通道时，他们的毛束偏转。由IHC产生的受体电位促进神经递质在其突触末端的释放。然而，OHC产生的受体电位为其运动活动提供了输入。OHC的体细胞运动性通常被认为是哺乳动物耳蜗放大的原因。OHC主要由起源于脑干的传出纤维支配。由ACh的释放介导的传出动作的效果可以改变耳蜗分区内的微机械事件，从而提供耳蜗放大器的“增益控制”。我们实验室的长期目标是研究OHC运动，毛细胞机械电转导，以及机械放大的机制。具体而言，我们的目标是：1）研究野生型和prestin突变小鼠OHC的力学特性; 2）研究电刺激传出激活对OHC受体电流和受体电位的影响; 3）研究成年IHC的力电转导。分离的小鼠OHC将用于目标1，而沙鼠半乳沙鼠制剂将用于目标2和目标3。半耳蜗制备将允许我们测量毛细胞受体电流（或受体电位）和BM运动同时在不同的耳蜗位置，而BM是机械刺激和/或传出终端电刺激。研究毛细胞的机械电和机电转换将有助于阐明感觉细胞在听觉中的功能。由于大多数美国听力损失患者（约3000万人）都有某种毛细胞损伤，因此了解毛细胞的运作对于生物补救和预防毛细胞相关的听力损失和耳聋至关重要。

DESCRIPTION (provided by applicant): 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.