MODULATION OF T-TYPE CA CHANNELS

描述(改编自申请人的描述)：本报告的目标 建议完善对其功能和分子的理解 T型钙通道的药理学。该实验方法利用 膜片钳技术在生物物理和第二信使调制研究中的应用 在前两个异源克隆的T型钙通道α1H和α1G中 在HEK 2993细胞中表达。有四个具体目标。具体目标1 确定介导花生四烯酸(AA)代谢的代谢物 阻断T型钙通道。具体目标2评估以下方面的贡献 PKC/G蛋白对T型钙通道的调节作用具体目标3定义了 构成特定异构体电流动力学基础的分子跃迁 了解信道调制机制。具体目标4建议确定 第二信使与T型钙通道相互作用的部位。

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.