REGULATION OF NA/K PUMP FUNCTION

NA/K 泵功能的调节

• 批准号: 3473066
• 负责人: JOSEPH R STIMERS
• 金额: $ 11.39万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473066
• 关键词: acidity /alkalinity; allosteric site; alpha adrenergic receptor; antiadrenergic agents; beta adrenergic receptor; biological models; calcium; cardiac glycosides; chick embryo; cyclic AMP; embryo /fetus cell /tissue; extracellular matrix; guanosine triphosphate; guinea pigs; heart cell; heart electrical activity; hormone regulation /control mechanism; hydrogen; hypokalemia; intracellular membranes; laboratory rat; magnesium deficiency; membrane activity; muscle cells; myocardial ischemia /hypoxia; neurotransmitters; ouabain; potassium; sodium; sodium potassium exchanging ATPase; voltage /patch clamp

The long range goal of this research project is to understand how the Na/K pump: 1) is physiologically regulated in its activity, sensitivity to cardiac glycosides and site density; 2) is regulated pathophysiologically; and 3) is involved in the regulation of important role in maintaining ion gradients across the surface membrane of excitable cells and its role as the site of action of therapeutic agents (i.e., cardiac glycosides). It is also becoming apparent that normal cardiac activity and some pathological states (e.g., ischemia, hypokalemia and hypomagnesemia) alter Na/K pump function and/or sensitivity to glycosides. This project will study isolated cardiac muscle cells from embryonic chick, rat and guinea pig with the patch clamp technique in conjunction with selected use of microspectrofluorometry. Since the literature contains reports on Na/K pump function and glycoside sensitivity which vary widely for each species and between species, the use of 3 species will provide valuable control data which will clarify these apparent differences in regulation of Na/K pump function. The proposed experimental protocols will provide new information about factors which 1) regulate Na/K pump function and 2) alter glycoside sensitivity. Specifically, the actions of Na, K, Ca and H ions (both intra- and extra-cellular) and cardioactive agents (e.g., neurotransmitters) on Na/K pump studied. Furthermore, how Na/K pump function in cardiac muscle might adapt to pathophysiological states (e.g. hypokalemia) will be investigated in experiments designed to measure Na/K pump function in preparations which have been cronically altered (e.g. growth in low K medium). These experiments will provide new information on the pathophysiology of Na/K pump function.

该研究项目的远距离目标是了解NA/K如何 泵：1）在生理上受到其活性的调节，对 心脏糖苷和位点密度； 2）受到病理生理的调节； 3）参与了维持离子的重要作用的调节 可激发细胞的整个表面膜的梯度及其作用 治疗剂的作用部位（即心脏糖苷）。 这是 同样显而易见的是正常的心脏活动和一些病理 状态（例如缺血，低核血症和低磁性血症）改变Na/k泵 功能和/或对糖苷的敏感性。 该项目将研究胚胎小鸡的孤立心肌细胞， 大鼠和豚鼠与斑块夹技术结合 选择微光谱荧光测定法。 由于文学包含 关于Na/K泵功能和糖苷灵敏度的报告 对于每个物种，物种之间，将使用3种物种提供 有价值的控制数据将阐明这些明显的差异 Na/K泵功能的调节。 提出的实验协议将 提供有关哪些因素的新信息1）调节Na/k泵功能 2）改变糖苷敏感性。 具体而言，NA，K，CA的行为 和H离子（包括细胞内和细胞外）和心活性剂（例如， Na/k泵的神经递质）研究。 此外，Na/k泵如何 心肌的功能可能适应病理生理态（例如 低钾血症将在旨在测量Na/K的实验中研究 泵的功能在狂暴改变的制剂中（例如 低k培养基的生长）。 这些实验将提供有关的新信息 Na/K泵功能的病理生理学。