PROPERTIES AND FUNCTIONS OF CA CHANNELS IN HAIR CELLS

毛细胞中 CA 通道的特性和功能

• 批准号: 6626871
• 负责人: EBENEZER N YAMOAH
• 金额: $ 23.83万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626871
• 关键词: Rana; actins; calcium channel; calcium channel blockers; calcium flux; chickens; cochlea; ear hair cell; ear pharmacology; magnesium ion; neurotransmitter transport; potassium channel; protein isoforms; voltage /patch clamp; voltage gated channel

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.

描述：（改编自研究者摘要）听力损失影响 数千万美国人。对于许多人来说，赤字 是由毛细胞受损引起的毛细胞是大脑内部的感觉细胞， 它们对我们欣赏声音和平衡感至关重要。 电压门控钙（Ca）通道（VGCC）在细胞内钙通道的形成中起着重要作用。 毛细胞功能事实上，听力和平衡障碍，例如梅尼埃氏 疾病，可能是由于VGCC功能障碍。通过VGCC的Ca内流 代表毛细胞中Ca的主要来源。先前的研究 表明毛细胞只表达L型钙通道，并得出结论， 这种钙通道亚型控制神经递质的释放和激活， 钾（K）通道，介导低级脊椎动物的电调谐。 然而，这些通道的性质，使钙的不同作用， 是未知的。与以前的调查相反， 通道亚型，我们最近获得的生理数据表明， 毛细胞可能表达一种以上的钙通道。 我们假设毛细胞可能表达两类钙通道（L-和 非L型通道）以产生多个Ca依赖性过程。而 L-型钙通道可能介导K通道的激活， 通道可以触发神经递质释放。或者，L型 通道可能介导诱发性神经递质释放，而非L型通道可能介导诱发性神经递质释放。 通道可能触发紧张性神经递质释放。然而，我们预测， 两种钙通道亚型的功能重叠， 类似的电压依赖性和两个通道的共定位。 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， actin）可能参与Ca通道的聚集。我们将检验这些假设， 使用牛蛙球囊和鸡基底乳头的毛细胞。 这些研究将提供有关Ca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以实现为我们的 了解钙通道的门控、渗透和药理学， 更明确。