PHARMACOLOGICAL ANALYSIS OF IONIC BALANCE IN HAIR CELLS

毛细胞离子平衡的药理学分析

• 批准号: 6124933
• 负责人: EDMUND A MROZ
• 金额: $ 30.61万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6124933
• 关键词: acidity /alkalinity; active transport; amiloride; bicarbonates; calcium channel; calcium flux; calcium transporting ATPase; cell morphology; chloride channels; ear hair cell; ear pharmacology; electrolyte balance; goldfish; guinea pigs; inhibitor /antagonist; ion transport; magnesium; membrane potentials; membrane transport proteins; neuropharmacology; phosphorus; sodium potassium exchanging ATPase; tissue /cell culture

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，取决于适当的离子 细胞外和细胞内的组合物。 头发的几种形式 细胞损伤和功能丧失（例如，梅尼埃听觉过度刺激 疾病、衰老）可能是由于失去适当的离子平衡造成的。 长期 目的是确定毛细胞如何调节其细胞内离子 status. 了解这些监管过程最终可能有助于 预防或减少某些形式的听力损失。 此前在这 项目，离子平衡的主要细胞过程，和净 测定了对照条件下分离株的转运率 金鱼毛细胞 在一个目标中，实验方法的组合 （电子探针微量分析，显微荧光测定和定量 显微镜）和理论分析将被用来确定如何这些 这些过程在完整的细胞中一起工作。 关于交通运输如何 在不同的扰动条件下， 将进行离子传输过程。 从下列结果推断 溶质和调节过程之间的特定主要相互作用 参与维持电池稳态的过程。 这种预测的相互作用将在进一步的实验中进行测试。 第二 aim将离子平衡的分析扩展到更自然的状态：毛细胞 将在下图中检查顶部定位的转导通道打开的情况。 顶侧与基底侧不同液体的条件 这些细胞的表面，就像在体内一样。 该提案将测试 关于这些通道的存在和组成的假设 内淋巴液可能会影响离子的动力学 调控 此外，这种实验方法将用于进一步的研究。 溶质运输过程之间相互作用的测试。 第三个目标是检验哺乳动物外毛细胞具有 在满足一些酸/碱的挑战，可能是由于他们的困难， 听觉传导的膜特化。 发现一辆 令人惊讶的是，金鱼毛细胞的代谢负荷中有很大一部分是 致力于调节酸碱平衡。 理论研究表明， 具有高的泄漏和泵送酸的速率可能是有利的。 如果是这样的话，那么哺乳动物（豚鼠）的外毛细胞似乎没有这种功能。 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 对离子平衡的某些类型的挑战特别敏感。