PROPERTIES AND FUNCTIONS OF CA CHANNELS IN HAIR CELLS

毛细胞中 CA 通道的特性和功能

基本信息

批准号：
6342350
负责人：
EBENEZER N YAMOAH
金额：
$ 22.27万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
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/6342350
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

项目摘要

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。对于其中许多人来说，赤字由毛细胞损伤引起。毛细胞是内脏的感觉细胞车;它们对于我们欣赏声音和保持平衡感至关重要。电压门控钙 (Ca) 通道 (VGCC) 在毛细胞功能。事实上，听力和平衡障碍，例如美尼尔氏疾病，可能是由于 VGCC 功能障碍所致。 Ca 通过 VGCC 流入代表毛细胞中 Ca 的主要来源。之前的研究有表明毛细胞仅表达 L 型 Ca 通道并得出结论：这种 Ca 通道亚型控制神经递质的释放和激活钾 (K) 通道，介导低等脊椎动物的电调谐。然而，这些通道的特性使得 Ca 具有不同的作用未知。与之前的研究相反，该研究表明单个 Ca 通道亚型，我们最近获得的生理数据表明毛细胞可能表达不止一种类型的 Ca 通道。我们假设毛细胞可能表达两类 Ca2+ 通道（L- 和非L型通道）产生多个Ca依赖性过程。鉴于 L 型 Ca 通道可能介导 K 通道的激活，L 型通道可能会触发神经递质释放。或者，L 型通道可能介导诱发的神经递质释放，而非 L 型通道可能会触发强直性神经递质的释放。然而，我们预测由于以下原因，两种 Ca 通道亚型将存在功能重叠相似的电压相关特性和两个通道的共定位。我们进一步假设 Ca 通道簇可能由多个通道子类型。最后，我们假设膜细胞骨架（例如肌动蛋白）可能参与 Ca 通道聚集。我们将测试这些假设，使用来自牛蛙球囊和鸡基底乳头的毛细胞。这些研究将为 Ca 的特性提供宝贵的信息。赋予毛细胞功能的通道。通过这些研究，理性 Ca通道亚型特异性药物的设计可能会随着我们的研究而实现对 Ca 通道的门控、渗透和药理学的理解变得更明确。