MODULATION OF T-TYPE CA CHANNELS

描述（改编自申请人的描述）：本申请的目标 建议是完善对功能和分子的理解 T型钙通道药理学。实验方法利用了 膜片钳技术用于研究生物物理学和第二信使调节 前两个克隆的T型钙通道，α 1H和α 1G， 在HEK 2993细胞中表达。有四个具体目标。具体目标1 确定了花生四烯酸（AA）代谢的代谢产物， 阻断T型钙通道。具体目标2评价了 PKC/G蛋白对T型钙通道的调节作用具体目标3定义了 作为异构体特异性电流动力学基础的分子跃迁， 了解频道调制的机制。具体目标4提出， 第二信使与T型钙通道相互作用的位点。

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.