MODULATION OF T-TYPE CALCIUM CHANNELS

T型钙通道的调制

• 批准号: 6097499
• 负责人: Jonathan Satin
• 金额: $ 27.88万
• 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/6097499
• 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（改编自申请人的描述）：此目标 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 膜片钳技术研究生物物理学和第二信使调制 前两个克隆的 T 型 Ca 通道 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 鉴定介导花生四烯酸 (AA) 代谢的代谢物 阻断 T 型 Ca 通道。具体目标 2 评估的贡献 T 型 Ca 通道的 PKC/G 蛋白调节。具体目标 3 定义了 异构体特异性电流动力学基础的分子转变 访问信道调制机制。具体目标 4 建议确定 第二信使和T型Ca通道之间相互作用的位点。