FUNCTION AND ASSEMBLY OF K+ CHANNELS IN T LYMPHOCYTES

T 淋巴细胞 K 通道的功能和组装

• 批准号: 2701647
• 负责人: Carol J Deutsch
• 金额: $ 33.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2701647
• 关键词: T lymphocyte; apoptosis; cell biology; cell free system; cell morphology; gene expression; human tissue; lasers; membrane potentials; potassium channel; protein biosynthesis; protein structure function; tissue /cell culture; transfection; voltage /patch clamp

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.

这项研究计划提出要研究生物物理性质和 电压门控性钾通道的亚基相互作用及其在心肌细胞中的作用 T淋巴细胞生理学。这项建议分为三个主要部分 项目。第一个方案确定K+通道选通的影响， 膜电位的失活动力学和累积失活， 调节量减少，并导致细胞凋亡。威勒型和突变型K+ 通道将在小鼠T细胞系CTLL-2中异源表达， 缺乏内源性K+通道。第二个项目决定营业额 功能性K+通道异构体的速率及其生理影响 人原代T淋巴细胞K+通道的不可逆性消融这 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和 抑制T细胞电压门控K+通道，特别是Kv1.3，in 体外无细胞Ad细胞表达系统。这将需要 野生型和截短型K+通道DNA序列的表达。