REGULATION OF NA/K PUMP FUNCTION

本研究项目的长期目标是了解Na/K 泵：1）在其活动，敏感性， 强心苷和位点密度; 2）在病理生理学上受到调节; 和3）参与调节维持离子的重要作用 梯度穿过可兴奋细胞的表面膜， 治疗剂的作用部位（即，强心苷）。 是 正常的心脏活动和一些病理性的 状态（例如，缺血、低钾血症和低镁血症）改变Na/K泵 功能和/或对糖苷的敏感性。 本项目将研究从鸡胚中分离的心肌细胞， 用膜片钳技术结合 选择使用显微荧光光谱法。 由于文献中包含 关于Na/K泵功能和糖苷敏感性的报告， 对于每个物种和物种之间，使用3个物种将提供 有价值的控制数据，将澄清这些明显的差异， Na/K泵功能的调节。 拟议的实验方案将 提供了有关1）调节Na/K泵功能的因素的新信息 （2）改变糖苷敏感性。 具体来说，Na、K、Ca 和H离子（细胞内和细胞外）和心脏活性剂（例如， 神经递质）对Na/K泵的影响。 此外，Na/K泵 心肌的功能可能适应病理生理状态（例如， 低钾血症）将在旨在测量Na/K的实验中进行研究 在已经被慢性改变的制剂中的泵功能（例如， 低K培养基中生长）。 这些实验将提供新的信息 Na/K泵功能的病理生理学。

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.