PH REGULATION IN VENTRICULAR CELLS

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The electrical and mechanical properties of mammalian ventricular muscle are markedly affected by changes in local pH. This sensitivity may significantly contribute to the myocardial dysfunction accompanying ventricular ischemia. Hence, the cellular systems for controlling the intracellular acid-base status of ventricular muscle are critically important for maintenance of normal heart function. The mechanism of intracellular pH (pH1) regulation and its modulation by membrane potential and hormones is unresolved in mammalian ventricular muscle and is the principal focus of this project. The secondary objective is to quantify the relationship between pH and contraction. To avoid the problems associated with multicellular cardiac preparations, all experiments will be conducted on single ventricular cells. Fluorescent dyes and ion-selective-microelectrodes will be used to measure intracellular activities of H+, Na, Cl, HCO3 and Ca in individual cells. Membrane potential will be controlled using whole-cell patch clap techniques and a recently developed rapid perfusion system will be used to change external solution composition within 7 msec. Cell contraction will be monitored with a newly developed video motion detector. The results are expected to provide new insight into the ionic requirements, hormonal control and"voltage sensitivity of pH, regulatory systems in mammalian ventricular muscle. The results should also yield new information, obtained under physiologically realistic conditions, concerning the pH1- contraction relationship in ventricular muscle.