MODULATION OF T-TYPE CA CHANNELS

T 型 CA 通道的调制

• 批准号: 6537683
• 负责人: Jonathan Satin
• 金额: $ 25.34万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6537683
• 关键词: G protein; anandamide; arachidonate; binding sites; biophysics; calcium channel; calcium flux; cardiovascular system; cell line; chemical kinetics; electrophysiology; guanine nucleotide binding protein; membrane activity; neurotransmitters; oxidative stress; pharmacology; phosphorylation; protein isoforms; protein kinase C; protein structure function; site directed mutagenesis; structural biology; superoxides; voltage /patch clamp; voltage gated channel

DESCRIPTION (adapted from the applicant's description): The goal of this proposal is to refine the understanding of the function and molecular pharmacology of T-type Ca channels. The experimental approach utilizes the patch clamp technique to study the biophysics and second messenger modulation of the first two cloned T-type Ca channels, alpha1H and alpha1G, heterologously expressed in HEK 2993 cells. There are four specific aims. Specific aim 1 identifies the metabolites of arachidonic acid (AA) metabolism that mediate blockade of T-type Ca channels. Specific aim 2 evaluates the contribution of PKC/G protein modulation of T-type Ca channels. Specific aim 3 defines the molecular transitions that underlie isoform-specific current kinetics and access the mechanism of channel modulation. Specific aim 4 proposes to identify the sites of the interaction between second messengers and T-type Ca channels.

描述（根据申请人的描述改编）：目的 建议是完善对功能和分子的理解 T型CA通道的药理学。实验方法利用 贴片夹技术研究生物物理学和第二信使调制 在前两个克隆的T型CA通道中，Alpha1h和Alpha1g异源 在HEK 2993细胞中表达。有四个具体目标。具体目标1 识别介导的花生四烯酸（AA）代谢的代谢产物 T型CA通道的封锁。特定目标2评估 T型Ca通道的PKC/G蛋白调制。特定目标3定义了 分子过渡是基础的同类特异性电流动力学和 访问通道调制的机制。特定目的4提议识别 第二使者和T型CA通道之间相互作用的位点。