ION CHANNEL CONTROL BY CALCIUM

通过钙控制离子通道

• 批准号: 3404259
• 负责人: DARRELL V LEWIS
• 金额: $ 10.4万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404259
• 关键词: action potentials; calcium; cations; cyclic AMP; electrophysiology; epilepsy; ion transport; membrane permeability; membrane potentials; neural conduction; neurons; neurotransmitters; tetraethylammonium compound; tissue /cell culture

Our goal is to determine how the level of free intracellular calcium, (Ca)i, affects the opening and closing kinetics of several important ionic channels in neurons. The conductances, and corresponding channels, studied will be 1) voltage sensitive calcium conductance or gCa, 2) calcium activated cation conductance or gCATca, 3) calcium activated potassium conductance or gKca. The neurons studied will be identified neurons of Aplysia californica in cell culture. The preparation and species has been chosen because we have evidence from prior studies that the above named conductances are present and are important determinants of excitability in these neurons. Channel kinetics will be measured using patch clamping and single channel analysis techniques. The neurons in culture are more amenable to patch clamping than in situ. The specific aims are 1) to determine whether increased (Ca)i reduces the probability of opening of calcium channels, 2) to characterize the gCATca channels that seem to be present on the majority of Aplysia neurons, and 3) to determine how many subtypes of gKca channels are found on these neurons and how they differ in their kinetics and sensitivity to tetraethylammonium ion. This informaton may help clarify how (Ca)i regulates neuronal excitability. This knowledge could have applications in clinical conditions where effects of calcium on neuronal function are believed to be relevant such as epilepsy and anoxic-ischemic damage.

我们的目标是确定自由细胞内钙的水平， （Ca）i影响几种重要离子的开口和关闭动力学 神经元中的通道。 导电和相应的通道研究 将为1）电压敏感钙电导或GCA，2）钙 活化的阳离子电导或GCATCA，3）钙激活钾 电导或GKCA。 研究的神经元将被鉴定出 加利福尼亚州的Aplysia在细胞培养中。 制剂和物种已经 之所以选择，是因为我们有先前研究的证据表明上述命名 电导率存在，并且是兴奋性的重要决定因素 这些神经元。 通道动力学将使用斑块夹具和 单通道分析技术。 文化中的神经元更多 比原位适合贴片夹具。 具体目的是1） 确定增加（CA）我是否降低了打开的可能性 钙通道，2）表征似乎是GCATCA通道 出现在大多数Aplysia神经元上，3）确定多少 在这些神经元上发现了GKCA通道的亚型，以及它们如何不同 它们的动力学和对四乙基铵离子的敏感性。 这个信息 可能有助于阐明（CA）如何调节神经元兴奋性。 这个知识 可以在钙对钙对 据信神经元功能是相关的，例如癫痫和 缺氧 - 缺血损害。