PHARMACOLOGICAL ANALYSIS OF IONIC BALANCE IN HAIR CELLS

毛细胞离子平衡的药理学分析

• 批准号: 3215478
• 负责人: EDMUND A MROZ
• 金额: $ 17.34万
• 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 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3215478
• 关键词: active transport; adenosinetriphosphatase; aminoacid transport; biological signal transduction; calcium channel; ear hair cell; electrolyte balance; electron probe spectrometry; electrophysiology; fluorimetry; fresh water environment; goldfish; guinea pigs; ion transport; mathematical model; membrane channels; membrane permeability; membrane potentials; membrane transport proteins; model design /development; pharmacology; potassium channel; sodium channel

The proper functioning of hair cells, the sensory transducing cells of the auditory and vestibular systems, depends on proper ionic compositions both outside and inside those cells. Although much is known about the composition of fluids outside hair cells, little is known about ions inside hair cells or the processes that regulate them. Permanent damage to hair cells is a major cause of deafness. Most processes leading to injury of hair cells are poorly understood. In some circumstances, the natures of the insult and of the resulting injury suggest loss of ionic balance, and consequent loss of the hair cell's ability to regulate its volume, as possible causes of damage. The long-term objective of this project is to understand the cellular mechanisms that determine ionic balance in hair cells. this understanding would fill a major gap in knowledge about the normal physiology of hair cells. It would ultimately allow critical examination of the role of loss of ionic balance in the pathophysiology of hair cells. In this project, new information will be obtained about the cellular mechanisms of ionic balance in hair cells. In particular, electrically silent transporters and active ion transporters will be studied quantitatively in hair cells for the first time. Isolated hair cells will be subjected to pharmacological treatments that specifically affect mechanisms known to influence ionic balance in hair cells or in other cells. The ionic content of hair cells will be determined by electron probe microanalysis, providing both composition and net ion transport rates. Ionic activities (or "free" concentrations) will be determined by quantitative microfluorometry of ion-specific dyes, providing information about intracellular binding or sequestration of ions. Measurements of membrane potential will provide information about its influence on ionic transport during these treatments. By the end of the first three years, these studies should determine the quantitative importance of several major ionic channels, transporters, and pumps involved in ionic balance in hair cells. In later years, these findings will be extended to the situation in vivo, where different fluids bathe the apical and basolateral membranes of the hair cell. Ultimately, it will become possible to examine the role of ionic balance in specific issues in auditory physiology and pathophysiology, particularly with respect to temporary threshold shifts, acoustic trauma, ototoxicity, Meniere's disease, and aging.

毛细胞的正常功能，感觉传导细胞 听觉和前庭系统，取决于适当的离子成分 在这些牢房外面和里面。尽管人们已经知道了很多关于 毛细胞外液体的组成，对毛细胞内的离子知之甚少 毛细胞或调节毛细胞的过程。 毛细胞的永久性损伤是导致耳聋的主要原因。多数 导致毛细胞损伤的过程知之甚少。在一些 情况、侮辱的性质以及由此造成的伤害 暗示离子平衡的丧失，以及由此导致的毛细胞的丧失 有能力调节其音量，作为可能的损坏原因。 这个项目的长期目标是了解细胞 决定毛细胞离子平衡的机制。这一理解 将填补有关头发正常生理知识的一大空白 细胞。它最终将允许对损失的作用进行批判性的审查 毛细胞病理生理学中的离子平衡。 在这个项目中，将获得关于细胞的新信息 毛细胞中离子平衡的机制。尤其是在电气方面， 沉默的转运蛋白和活性的离子转运蛋白将被研究 首次在毛细胞中进行了定量检测。分离的毛细胞将 接受药物治疗，这种治疗特别影响 已知的影响毛细胞或其他细胞离子平衡的机制 细胞。毛细胞的离子含量将由电子决定。 探针微量分析，提供成分和净离子传输 费率。离子活度(或“自由”浓度)将由下列因素决定 离子特定染料的定量显微荧光测定法，提供信息 关于细胞内离子的结合或隔离。测量 膜电位将提供有关其对离子的影响的信息 在这些治疗过程中的运输。在头三年结束时， 这些研究应该确定以下几个主要因素的数量重要性 参与头发离子平衡的离子通道、转运体和泵 细胞。 在以后的几年里，这些发现将扩展到体内的情况， 其中不同的液体沐浴在根尖和基底外侧的膜上 毛细胞。最终，我们将有可能考察 听觉生理学和声学中的离子平衡 病理生理学，特别是关于临时性阈值偏移， 听觉创伤、耳毒性、梅尼埃病和衰老。