PROPERTIES AND FUNCTIONS OF CA CHANNELS IN HAIR CELLS

描述：(改编自《调查者摘要》)听力损失影响 数千万美国人。对于这些人中的许多人来说，赤字 是毛细胞受损引起的。毛细胞是身体内部的感觉细胞 汽车；它们对我们欣赏声音和平衡感是必不可少的。 电压门控性钙通道(VGCC)在钙离子通道中发挥重要作用 毛细胞的功能。事实上，听力和平衡障碍，如梅尼埃病 疾病，可能是由于VGCC功能障碍引起的。钙离子通过VGCC流入 代表毛细胞中钙的主要来源。之前的研究已经 提示毛细胞只表达L型钙通道，并得出结论 这种钙通道亚型控制着神经递质的释放和激活。 钾(K)通道，在低等脊椎动物中调节电调。 然而，这些渠道的性质，使不同的作用 都是未知的。与之前的调查相反，即只有一个案例 通道亚型，我们最近获得的生理数据表明 毛细胞可能表达多种类型的钙通道。 我们推测毛细胞可能表达两类钙通道(L和 非L型通道)，产生多个钙依赖过程。鉴于 L型钙通道可能介导L型钾通道的激活 通道可能触发神经递质的释放。或者，L式的 经络可能介导诱发的神经递质释放，而非L型 通道可能触发紧张性神经递质的释放。然而，我们预测， 由于以下原因，两种钙通道亚型将会有功能重叠 类似的电压依赖特性和两个通道的共局域化。 我们进一步假设，钙通道簇可能由一个以上的 通道子类型。最后，我们假设膜细胞骨架(例如：膜细胞骨架)可能与细胞骨架有关。 肌动蛋白)可能参与了钙通道聚集。我们将检验这些假设， 使用牛蛙球囊和鸡基底乳头中的毛细胞。 这些研究将提供关于钙的性质的宝贵信息 赋予毛细胞功能的通道。通过这些研究，理性 钙通道亚型特异性药物的设计可实现为OUR 对钙通道的门控、渗透和药理学的理解 更清晰的定义。

DESCRIPTION: (Adapted from the Investigator's Abstract) Hearing loss affects tens of millions of Americans. For many of these individuals, the deficit arises from damage to hair cells. Hair cells are the sensory cells of the inner car; they are essential for our appreciation of sound and our sense of balance. Voltage-gated calcium (Ca) channels (VGCC) play several important roles in hair-cell functions. In fact, hearing and balance disorders, e.g. Meniere's disease, may result from VGCC dysfunction. Ca influx through the VGCC represents the principal source of Ca in hair cells. Previous studies have suggested that hair cells express only L-type Ca channels and concluded that this Ca channel subtype controls neurotransmitter release and activation of potassium (K) channels, which mediate electrical tuning in lower vertebrates. However, the properties of these channels, which render the diverse roles of Ca are unknown. Contrary to previous investigations that suggested a single Ca channel subtype, we have recently obtained physiological data which suggest that hair cells may express more than one type of Ca channel. We hypothesize that hair cells may express two classes of Ca channels (L- and non-L-type channels) to produce multiple Ca-dependent processes. Whereas the L-type Ca channels may mediate the activation of K channels, the L-type channels may trigger neurotransmitter release. Alternatively, the L-type channel may mediate evoked neurotransmitter release while the non L-type channel may trigger tonic neurotransmitter release. However, we predict that there will be functional overlap of the two Ca channel subtypes because of similar voltage-dependent properties and co-localization of the two channels. We further hypothesize that Ca channel clusters may consist of more than one channel subtype. Finally, we hypothesize that membrane cytoskeleton (e.g. actin) may be involved in Ca channel clustering. We will test these hypotheses, using hair cells from the bullfrog saccule and chicken basilar papilla. These studies will provide invaluable information on the properties of Ca channels that confer hair cell functions. Through these studies, rational design of Ca channel subtype-specific drugs may be realized as our understanding of the gating, permeation and pharmacology of Ca channels becomes more defined.