REGULATION OF NA/K PUMP FUNCTION

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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.