BIOPHYSICS AND DEVELOPMENT OF COCHLEAR OUTER HAIR CELLS

描述：(根据申请者的摘要改编)：外毛细胞(OHC)是哺乳动物听力器官中的两个受体细胞之一， 在听力方面起着至关重要的作用。毛囊增强基底膜运动 通过耳蜗内的局部机械反馈过程，称为 “耳蜗放大器”。一般认为，人工耳蜗术的基础是 放大是毛细胞的一种电压依赖性的体细胞长度变化。这 扩增过程显然是高灵敏度、广泛性的原因 动态范围、精致的频率选择性和大量的非线性 在正常耳朵中可以看到的行为。该提案的长期目标是 研究毛细胞的发展和生物物理学。具体来说，我们的目标是：1) 通过同时记录膜电导来确定OHC膜电导如何影响运动响应的动态特性 同时影响运动响应的动态特性 记录膜电位变化和运动性的组合 全细胞电压钳和微室技术在豚鼠体内的应用 2)以确定机械载荷和初始单元长度如何影响 OHC运动的幅度、频率响应特性和不对称性， 用微室技术分离豚鼠耳蜗毛细胞。3)至 研究钾电导在三者之间的表达差异 一排排的OHC，使用全电池电压钳位技术对新开发的 沙土鼠半草制剂。4)确定OHC钾电流如何 出生后发育，使用全细胞电压钳技术在 半草制剂。5)确定脑功能是否成熟 OHC ACh受体受传出神经调节。这些实验将是 使用全电池电压钳制技术对从以下来源获得的OHC进行 科尔蒂器官的组织培养，去掉传出神经。这个 将在全电池电压钳制技术下进行实验 从Corti器官的组织培养中获得的去传出的PHC 神经支配。新生的蒙古沙土鼠被选为这两种发育的动物 研究表明，毛细胞发育的一个重要时期发生在出生后。 研究毛细胞的发展和生物物理学将勾勒出运动功能 这些假定的效应器，因此将导致更好地理解 它们在耳蜗力学中的作用。因为大多数美国人 听力损失，总共约3000万人，有某种毛细胞损伤， 了解OHC的运作对于生物修复是至关重要的 以及预防毛细胞相关的听力损失和耳聋。

DESCRIPTION: (Adapted from applicant's abstract): The outer hair cell (OHC) is one of two receptor cells in the mammalian hearing organ, the organ of Corti, and plays a critical role in hearing. OHCs enhance basilar membrane motion through a local mechanical feedback process within the cochlea, termed the 'cochlear amplifier'. It is generally believed that he basis of cochlear amplification is a voltage-dependent somatic length change of OHCs. This amplification process is apparently responsible for high sensitivity, broad dynamic range, exquisite frequency selectivity, and a host of nonlinear behaviors seen in the normal ear. The long-term goal of the proposal is to study the development and biophysics of OHCs. Specifically, our aims are: 1) to determine how OHC membrane conductances influence the dynamic characteristics of motile responses by simultaneously recording membrane conductances influences the dynamic characteristics of motile responses by simultaneously recording membrane potential changes and motility with a combination of whole-cell voltage-clamp and microchamber techniques in isolated guinea pig OHCs 2) to determine how mechanical load and initial cell length affect the magnitude, frequency response characteristics, and asymmetry of OHC motility, using microchamber technique with OHCs isolated from Guinea pig cochleae. 3) To study how potassium conductances are differentially expressed among the three rows of OHCs, using whole cells voltage clamp techniques on the newly developed gerbil hemicochlea preparation. 4) To determine how OHC potassium currents develop after birth, using whole-cell voltage-clamp technique on the hemicochlea preparation. 5) To determine whether the functional maturation of OHC ACh receptors is regulated by efferent innervation. The experiments will be carried out with whole-cell voltage-clamp techniques on OHCs obtained from tissue cultures of the organ of Corti, deprived of efferent innervation. The experiments will be carried out with whole cell voltage clamp techniques on PHCs obtained from tissue cultures of the organ of Corti, deprived of efferent innervation. Neonatal Mongolian gerbils are chosen for the two development studies, since an important period of hair cell development occurs after birth. Studying development and biophysics of OHCs will delineate the motor function of these putative effectors and thus, will lead to a greater understanding of their role in cochlear mechanics. Because the majority of Americans with hearing loss, some 30 million in all, have some kind of hair cell damage, understanding the operation of OHCs is essential to the biological remediation and prevention of hair cell-related hearing loss and deafness.