PHARMACOLOGICAL ANALYSIS OF IONIC BALANCE IN HAIR CELLS

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 无论是在细胞内外 一些侮辱头发的性质 细胞和由此产生的损伤表明， 毛细胞的变化可能涉及适当离子平衡的丧失（例如，在 暂时性听阈偏移、声损伤、耳毒性、梅尼埃病 疾病和衰老）。失去离子平衡会阻止正常的毛细胞 功能，并可能导致永久性损伤，例如，如果头发 细胞因此失去调节细胞体积的能力。 由于损害 毛细胞是耳聋的常见原因，了解离子 毛细胞的平衡过程可能最终有助于防止或减少 听力损失的类型 这个项目的长期目标是确定毛细胞如何 调节细胞内离子状态。 这些信息将填补一个 毛细胞和意志的正常生理知识的主要差距 最终有助于评估离子平衡的丧失是否起作用 在病理生理学上。 实验方法是对分离的毛细胞进行处理 旨在影响特定的细胞机制， 平衡 然后用电子探针微量分析法测定离子 毛细胞的组成和净离子转运率。 该方法 允许定量研究电动沉默运输和主动 离子泵很难用其他技术来研究。 定量 离子特异性染料的显微荧光测定法将提供进一步的信息 关于细胞内离子的结合或隔离， 进入毛细胞。 细胞体积将采用定量 视频显微镜 将测定膜电位的变化。 下一个项目期间的工作将解决基本问题， 关于单个离子传输过程的动态相互作用 在细胞中建立离子平衡。 实验将检验 钠、钾、氯、钙和氢离子， 它们穿过毛细胞膜的主要途径， 在细胞内外的浓度，对能源， 动力离子运输和膜电位。 成效为何 细胞内钙离子和氢离子处理实验 将被确定。 因为我们将测量所有主要的永久细胞 在这些实验中，我们也将能够发现意想不到的 离子平衡过程之间的相互作用。 除了 他们的重要性，了解基本的毛细胞生理学，这些 研究将为未来的发展奠定坚实的技术和知识基础。 工作，以评估毛细胞离子平衡的改变， 不同形式的听力损失。

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. The nature of some insults to hair cells and of the resulting injuries suggest that pathophysiological changes to hair cells can involve loss of proper ionic balance (e.g., in temporary threshold shifts, acoustic trauma, ototoxicity, Meniere's disease, and aging). Loss of ionic balance would prevent normal hair cell function, and could lead to permanent damage, if for example, the hair cell consequently lose the ability to regulate cell volume. Since damage to hair cells is a frequent cause of deafness, understanding the ionic balance processes of hair cell may eventually help to prevent or minimize some forms of hearing loss. The long-term objective of this project is to determine how hair cells regulate their intracellular ionic state. This information will fill a major gap in knowledge about the normal physiology of hair cells and will eventually help to evaluate whether loss of ionic balance plays a role in pathophysiology. The experimental approach is to subject isolated hair cells to treatments designed to affect specific cellular mechanism that influence ion balance. Electron-probe microanalysis is then used to determine ion composition and net ion-transport rates of hair cells. This method allows quantitative stud of electrically silent transporters and active ion pumps that are hard to study with other techniques. Quantitative microfluorometry of ion-specific dyes will provide further information about intracellular binding or sequestration of ions once they have entered the hair cells. Cell volume will be measured with quantitative video microscopy. Changes in membrane potential will be determined. Work during the next project period will address fundamental questions about the individual ion-transport processes whose dynamic interactions establish ion balance in the cell. Experiments will examine how flows of sodium, potassium, chloride, calcium, an d hydrogen ion, through each of their major pathways across the hair-cell membrane, depend on ion concentration inside and outside the cell, on the energy sources that power ion transport, and on the membrane potential. The effects of these experiments on the intracellular handling of calcium and hydrogen ions will be determined. Since we will measure all the major permanent cell ions in these experiments, we will also be able to discover unexpected interactions among the individual ion-balance processes. In addition to their importance for understanding basic hair-cell physiology, these studies will forming a solid technical and intellectual basis for future work to evaluate the role of alterations of hair-cell ion balance in different forms of hearing loss.