ASSOCIATION OF KATP CHANNEL WITH SULFONYLUREA RECEPTOR

KATP 通道与磺酰脲受体的关联

• 批准号: 6385034
• 负责人: ANTONIO J CARRASCO
• 金额: $ 3.65万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6385034
• 关键词: adenosine triphosphate; biological signal transduction; cardiotonic agents; cardiovascular pharmacology; drug receptors; gene deletion mutation; immunoprecipitation; membrane channels; potassium channel; receptor sensitivity; sulfonylurea; voltage /patch clamp; yeast two hybrid system

Kir6.2, an inward rectifying ATP-sensitive K+ (KATP) channel, is an integral plasma membrane protein that transduces metabolic events into membrane potential changes within the cell. In pancreatic Beta-cells, KATP channels play a key role in glucose-induced insulin secretion. Moreover, KATP channels have roles in hormone secretion, nueurtotransmitter release, as well as cardioprotection during ischemic stress. Recently, Kir6.2 and the sulfonylurea receptor, SUR1, were found expressed in pancreatic Beta-cells, and reconstitute a functional KATP channel. However, the specific protein domains of Kir6.2 and SUR1 necessary for association, or the way local ATP levels are regulated in the channel microenvironment are unknown. The yeast two-hybrid system together with deletion mutant analysis will be used to determine the domains necessary for this association, as well as any possible interaction with regulatory proteins, such as adenylate kinase. Furthermore, electrophysiology, e.g., patch clamp, techniques will be used on COS cells transfected with various Kir6.2 and SUR1 mutated proteins to ascertain the physiological significance of such interactions. Therefore, this research project will focus on two aspects of Kir6.2: 1) characterizing specific domains necessary for its interaction with SUR1, and 2) determining the regulation of this interaction, as well as the overall regulation of this KATP channel. Thus, project increases the knowledge of basic and essential physiological processes, such as, insulin secretion and cardio- protection.

Kir6.2是一种向内整流ATP敏感的K+（KATP）通道，是一个 整体质膜蛋白将代谢事件转导 膜电位在细胞内变化。 在胰腺β细胞中， KATP通道在葡萄糖诱导的胰岛素分泌中起关键作用。 此外，KATP频道在激素分泌中起作用， 缺血性递质释放和心脏保护 压力。 最近，Kir6.2和磺酰脲受体SUR1是 在胰腺β细胞中发现并重建功能 KATP频道。 但是，Kir6.2和Sur1的特定蛋白质结构域 关联所必需的，或者在本地ATP级别的调节方式中所必需的 通道微环境未知。 酵母双杂交系统 与缺失突变分析一起确定 该协会所需的域以及任何可能 与调节蛋白的相互作用，例如腺苷酸激酶。 此外，电生理学，例如斑块夹，技术将是 用于用各种Kir6.2和Sur1转染的COS细胞进行突变 蛋白质以确定这种生理意义 互动。 因此，该研究项目将重点放在两个 Kir6.2：1）表征其必要的特定域 与SUR1的相互作用，以及2）确定对此的调节 相互作用以及该KATP通道的总体调节。 因此，项目增加了基本和基本的知识 生理过程，例如胰岛素分泌和心脏 - 保护。