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（IHCs）将听觉信息传递到大脑，而外毛细胞（OHCs）将机械信号放大，然后由内毛细胞转导。这两种类型的毛细胞对基底膜（BM）的振动做出反应，当它们的毛束偏转时，通过位于立体纤毛尖端的机械换能器通道产生换能器电流。ihc产生的受体电位促进了突触末端神经递质的释放。然而，OHCs产生的受体电位为它们的运动活动提供输入。OHCs的体运动性通常被认为是哺乳动物耳蜗放大的原因。OHCs主要受源自脑干的传出纤维支配。由乙酰胆碱释放介导的传出作用可以改变耳蜗隔墙内的微力学事件，从而为耳蜗放大器提供“增益控制”。我们实验室的长期目标是研究OHC运动，毛细胞的机电转导，以及机械放大的机制。具体而言，我们的目标是：1)研究野生型和预突变小鼠OHCs的力学特性；2)研究电刺激的传出激活对OHCs受体电流和受体电位的影响；3)研究成人ihc的机电转导。分离的小鼠ohc将用于Aim 1，沙鼠耳蜗制剂将用于Aim 2和Aim 3。当耳蜗受到机械刺激和/或传出终端受到电刺激时，半耳蜗制备将使我们能够同时测量毛细胞受体电流（或受体电位）和耳蜗不同位置的脑基运动。研究毛细胞的机电转导，有助于阐明感觉细胞在听觉中的功能。因为大多数听力损失的美国人，总共约有3000万人，都有某种形式的毛细胞损伤，了解毛细胞的运作对于生物修复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.