Sodium Calcium Exchange in Ventricular Myocardium

Bridge, John

Abstract

This project is designed to identify and examine the properties of the Na/Ca exchange in rabbit ventricular myocardium. The Na/Ca exchange will be identified as a process that, like the Na pump, is capable of producing net movement of intracellular sodium against its electrochemical gradient. Unlike the sodium pump, it is not inhibitable by acetyl strophanthidin (ACS) and is not coupled to the movement of potassium. From the net movement of Na and Ca that occurs when the Na/Ca exchange is stimulated in the presence of ACS the stoichiometry of the exchange will be deduced. This stoichiometry will be checked for thermodynamic consistency. The hypothesis that net ion movement via the Na/Ca exchange is determined by differences in the magnitude of the inwardly directed electrochemical gradients for Na and Ca will be subject to preliminary examination. Finally, in a collaborative series of investigations, the relationship between Na ion content and activity changes during sodium pump blockage will be examined to lay the foundation for future studies. Those experiments will be conducted with (a) rapid flow chambers and temperature jump methodology, (b) measured of ion contents using atomic absorption spectrophotometry and extracellular spaces using 3H-sucrose and suitable liquid scintillation spectrometry, (c) membrane potential and tension measurements using conventional techniques. Much of the data gathered in this project will be analyzed in terms of simply thermodynamic concepts and equations and also in terms of current understanding of the physiology of excitation contraction coupling in heart. The long term goals of this project are to understand the role that Na/Ca exchange plays in cardiac excitation contraction coupling. This project has health relevance insofar as it involves fundamental processes in cardiac function and as such is particularly relevant to understanding the mode of operation of therapeutic drugs, e.g., the cardiotonic steroids. Na/Ca exchange may also be of importance in regulating intracellular calcium in both secretory and smooth muscle cells. It is considered by some authorities to mediate hypertension by virtue of its role in regulating calcium in smooth muscle.