FUNCTION AND ASSEMBLY OF K+ CHANNELS IN T LYMPHOCYTES

该研究计划建议研究生物物理特性， 电压门控性K+通道亚基间的相互作用及其在细胞内的作用 T淋巴细胞的生理学 该提案分为三个主要部分 项目 第一个项目确定K+通道门控的影响， 膜电位失活动力学和累积失活， 调节性体积减少和凋亡。 Wile型和突变K+ 通道将在小鼠T细胞系，CTLL-2， 缺乏内源性K+通道 第二个项目决定营业额 功能性K+通道亚型的比率，以及 原代人T淋巴细胞中K+通道的不可逆消融。 这 将需要使用一种新技术，发色团辅助激光 失活 第三个项目评估特定的装配模型， 抑制T细胞电压门控K+通道，特别是Kv1.3， 无细胞AD体外细胞表达系统。 这将需要 野生型和截短的K+通道DNA序列的表达。

This research program proposes to study the biophysical properties and subunit interactions of voltage-gated K+ channels and their role in the physiology of T lymphocytes. This proposal is divided into three main projects. The first project determines the impact of K+ channel gating, inactivation kinetics and cumulative inactivation on membrane potential, regulatory volume decrease, and apoptosis. Wile-type and mutated K+ channels will be heterologously expressed in a mouse T cell line, CTLL-2, which lacks endogenous K+ channels. The second project determines turnover rates of functional K+ channel isoforms, and the physiological impact of irreversible ablation of K+ channels in primary human T lymphocytes. This will entail use of a new technique, chromophore-assisted laser inactivation. The third project evaluates specific models of assembly and suppression of T cell voltage-gated K+ channels, specifically, Kv1.3, in cell-free ad in vitro cellular expression systems. This will entail expression of wild-type and truncated K+ channel DNA sequences.