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PHARMACOLOGICAL ANALYSIS OF IONIC BALANCE IN HAIR CELLS

毛细胞离子平衡的药理学分析

基本信息

批准号：
6476051
负责人：
EDMUND A MROZ
金额：
$ 32.47万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-04-01 至 2003-11-30
项目状态：
已结题

项目摘要

DESCRIPTION: The proper function of hair cells, the sensory transducing cells of the auditory and vestibular systems, depends on proper ionic compositions both extracellular and intracellular. Several forms of hair cell injury and loss of function (e.g., acoustic overstimulation, Meniere's Disease, aging) may result from loss of proper ionic balance. The long-term objective is to determine how hair cells regulate their intracellular ionic status. Understanding these regulatory processes may eventually help to prevent or to minimize some forms of hearing loss. Previously in this project, the major cellular processes of ionic balance, and the net transport rates under control conditions, were determined for isolated goldfish hair cells. In one aim, a combination of experimental methods (electron-probe microanalysis, microfluorometry, and quantitative microscopy) and theoretical analysis will be used to determine how these processes work together in the intact cell. An examination of how transport rates and solute contents change after different disturbances of ion-transport processes will be conducted. An inference from the results of specific major interactions among the solutes and the regulatory processes involved in the maintenance of the steady state of the cell will be made. Such predicted interactions will be tested in further experiments. A second aim extends the analysis of ion balance to a more natural state: hair cells with apically located transduction channels open will be examined under conditions of a different fluids bathing the apical versus the basolateral surfaces of these cells, as is the case in vivo. The proposal will test hypotheses about how the presence of these channels and the composition of the endolymphatic fluid that bathes them may affect the dynamics of ion regulation. Further, this experimental approach will be used for further tests of interactions among solute-transport processes. A third aim will test the hypothesis that mammalian outer hair cells have a difficulty in meeting some acid/base challenges, perhaps due to their membrane specializations for auditory transduction. It was found that a surprisingly high fraction of the metabolic load of goldfish hair cells is devoted to regulating acid/base balance. Theoretical studies suggest that there may be an advantage to having a high rate of leaking and pumping acid. If so, then mammalian (guinea-pig) outer hair cells do not seem to have this advantage. These studies will determine the acid-handling characteristics of several types of hair cells, to see if mammalian outer hair cells are particularly sensitive to certain types of challenges to ionic balance.

描述：毛细胞的正常功能，感觉传导听觉和前庭系统的细胞，依赖于适当的离子包括胞外和胞内的成分。几种形式的头发细胞损伤和功能丧失(例如，声过度刺激、梅尼埃氏症) 疾病、衰老)可能是由于失去适当的离子平衡所致。长期的目的是确定毛细胞如何调节其细胞内离子状态。了解这些监管过程最终可能有助于防止或尽量减少某些形式的听力损失。在此之前项目，离子平衡的主要细胞过程，以及净在控制条件下，测定了分离的金鱼毛细胞。在一个目标上，实验方法的组合 (电子探针显微分析、显微荧光法和定量显微镜)和理论分析将被用来确定在完好无损的细胞中，各个过程协同工作。对运输方式的考察不同扰动后的速率和溶质含量的变化将进行离子传输过程。从……的结果得出的推论溶质和调控过程之间的特定主要相互作用参与维护电池的稳定状态会有所不同。这种预测的相互作用将在进一步的实验中得到检验。一秒钟 Aim将离子平衡的分析扩展到更自然的状态：毛细胞位于顶端的转导通道打开后，将在不同液体洗浴根尖和基底侧的条件这些细胞的表面，就像在体内的情况一样。这项提案将考验关于这些通道的存在和这些通道的组成的假设沐浴它们的内淋巴液可能会影响离子的动力学。监管。此外，这一实验方法将被用于进一步溶质运移过程中相互作用的测试。第三个目标将检验哺乳动物外毛细胞具有难以应对一些酸/碱挑战，可能是因为它们听觉传导的膜特化。结果发现，一种令人惊讶的是，金鱼毛细胞代谢负荷的比例很高致力于调节酸碱平衡。理论研究表明，具有较高的渗漏率和泵送酸率可能是一个优势。如果是这样的话，哺乳动物(豚鼠)的外毛细胞似乎就没有这个。优势。这些研究将确定酸处理特性几种类型的毛细胞，看看哺乳动物的外毛细胞是否对某些类型的离子平衡挑战特别敏感。