PHARMACOLOGICAL ANALYSIS OF IONIC BALANCE IN HAIR CELLS

毛细胞的正常功能，毛细胞的感觉传导细胞， 听觉和前庭系统，取决于适当的离子成分， 在细胞内外 虽然我们对这一点了解很多， 毛细胞外的液体成分，对内部的离子知之甚少 毛细胞或调节它们的过程。 毛细胞的永久性损伤是耳聋的主要原因。 最 导致毛细胞损伤的过程知之甚少。 在一些 （一）对当事人的陈述和证据的效力; 表明失去离子平衡，随之而来的是毛细胞的损失 调节其体积的能力，作为可能的损坏原因。 该项目的长期目标是了解细胞 决定毛细胞中离子平衡的机制。 这种理解 将填补关于头发正常生理学知识的一个主要空白 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，新的信息将获得有关细胞 毛细胞中离子平衡的机制。 特别地，电 将研究沉默转运蛋白和活性离子转运蛋白 毛细胞中的数量首次。 分离的毛细胞将 接受药物治疗， 已知影响毛细胞或其他细胞中离子平衡的机制 细胞 毛细胞的离子含量将由电子 探针微量分析，提供成分和净离子传输 rates. 离子活性（或“游离”浓度）将通过以下方法测定： 离子特异性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螯合。 测量 膜电位将提供关于其对离子的影响的信息。 在这些治疗过程中。 到头三年结束时， 这些研究应该确定几个主要的定量重要性， 离子通道、转运体和泵参与头发中的离子平衡 细胞 在以后的几年里，这些发现将扩展到体内的情况， 其中不同的液体浸泡在细胞的顶膜和基底膜上， 毛细胞 最终，将有可能审查 离子平衡在听觉生理学的具体问题， 病理生理学，特别是关于暂时性阈值偏移， 声损伤、耳毒性、梅尼埃病和衰老。

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.