BIOPHYSICS AND DEVELOPMENT OF COCHLEAR OUTER HAIR CELLS

描述：（改编自申请人的摘要）：外毛细胞（OHC）是 哺乳动物听觉器官（柯替氏器）中的两个感受细胞之一， 在听力中起着关键作用。OHC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耳蜗的基础 扩增是OHC的电压依赖性体细胞长度变化。这 放大过程显然是负责高灵敏度，广泛 动态范围，精致的频率选择性，以及大量的非线性 在正常耳朵中看到的行为。该提案的长期目标是 研究OHCs的发展和生物物理学。具体而言，我们的目标是：1） 确定OHC膜电导如何影响动态特性 通过同时记录细胞膜电导 同时影响运动反应的动态特性 记录膜电位变化和运动性， 离体豚鼠全细胞电压钳和微室技术 OHC 2）以确定机械负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， 采用微室技术分离豚鼠耳蜗外毛细胞。3)到 研究钾电导在这三种细胞中的差异表达 行的OHC，使用全细胞电压钳技术对新开发的 沙鼠半乳糖制剂。4)为了确定OHC钾电流 在出生后发育，使用全细胞电压钳技术， 半胱氨酸制剂。5)以确定是否功能成熟的 OHC ACh受体受传出神经支配调节。实验将是 用全细胞电压钳技术对从以下获得的OHC进行 Corti器官的组织培养物，剥夺传出神经支配。的 将用全电池电压钳技术进行实验， 从Corti器官的组织培养物中获得的PHCs，剥夺了传出神经 神经支配选择新生蒙古沙鼠进行这两种发育 研究，因为毛细胞发育的重要时期发生在出生后。 研究外毛细胞的发育和生物物理学将有助于阐明其运动功能 了解这些假定的效应子，从而将有助于更好地了解 它们在耳蜗力学中的作用因为大多数美国人 听力损失，大约有3000万人，有某种毛细胞损伤， 了解OHCs的运行对于生物修复至关重要 以及预防与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.