MECHANISMS OF IONIC CHANNEL ACTIVITY

离子通道活性机制

• 批准号: 3156406
• 负责人: KARL L MAGLEBY
• 金额: $ 14.73万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3156406
• 关键词: calcium metabolism; cell membrane; ion transport; magnesium; membrane permeability; membrane potentials; muscle cells; neurons; phosphorylation; sarcolemma; striated muscles

The overall purpose of this research proposal is to determine the properties and underlying kinetic mechanisms of two different ionic channels in cell membranes: the calcium-activated potassium channel and a voltage dependent chloride channel of large conductance. Currents that flow through single ionic channels in the sarcolemma of cultured rat skeletal muscle cells will be recorded under voltage clamp using the patch clamp technique. With this electrophysiological technique it is possible to study the kinetics of single channels by observing (through step changes in the current) when single channels open and close. The effects of Na, K, and Mg ions, step changes in [Ca] ion, and possible phosphorylation on the activity of the Ca-activated K channel will be characterized. The mechanism underlying the observation that openings of the Ca-activated K channel tend to occur in bursts will also be examined. The effect of membrane potential on activation, inactivation, and removal of inactivation for the voltage dependent C1 channel of large conduictance will also be characteized, as well as the permeability of this channelto various ions. The above data will be used to obtain information about the number of open and closed states, the mean lifetimes of the open and closed states, and the rate constants for transitions between the various states for each channel. These findings will then be used to develop a kinetic scheme for each channel. The Ca-activated K channel modulates repetitive firing in neurons and affects membrane potential and excitability in muscle. The C1 channel of large conductance would also affect membrane excitability. To understand the properties and function of nerve and muscle membranes, it will be necessary to understand the properties and mechanisms of these two channels. Understanding these channels may also help in understanding and treating nerve and muscle disease, as therapeutic agents and toxins often exert their specific effects on ionic channels in cell membranes.

本研究计划的总体目的是确定 两种不同离子的性质和潜在的动力学机制 细胞膜通道：钙激活钾通道和 大电导的电压依赖性氯离子通道。 电流 流经培养大鼠肌膜中的单一离子通道 使用贴片在电压钳下记录骨骼肌细胞 夹紧技术。 通过这种电生理学技术，可以 通过观察（通过阶跃变化）来研究单通道的动力学 在当前）单通道打开和关闭时。 Na、K 的影响 和 Mg 离子，[Ca] 离子的阶跃变化，以及可能的磷酸化 Ca 激活 K 通道的活性将被表征。 这 观察到 Ca 激活 K 的开口的机制 还将检查倾向于突发发生的信道。 的效果 激活、失活和去除失活时的膜电位 对于大电导的电压相关 C1 通道也将是 特征以及该通道对各种离子的渗透性。 上述数据将用于获取开放数量信息 和关闭状态，打开和关闭状态的平均寿命，以及 每个状态之间转换的速率常数 渠道。 然后，这些发现将用于开发动力学方案 每个频道。 Ca 激活的 K 通道调节重复放电 神经元并影响肌肉的膜电位和兴奋性。 C1 大电导的通道也会影响膜的兴奋性。 到 了解神经和肌肉膜的特性和功能， 有必要了解这两种物质的性质和机制 渠道。 了解这些渠道也可能有助于理解和 治疗神经和肌肉疾病，通常作为治疗剂和毒素 对细胞膜中的离子通道发挥其特定作用。