Maintenance of a constant cell volume is a fundamental physiological process shared by all living animal cells. In cardiac cells, which typically have a small volume/surface area ratio, the intracellular milieu is repeatedly disturbed by recurrent electrochemical and metabolic events which would affect cell volume were it not for the counteractivity of sarcolemmal transport pathways. In the ischemic myocardium, a critical factor early in the development of pathological changes is the loss of cell volume regulation (cell swelling). The recognized difficulties in measuring cell volume and ionic composition of intact cardiac muscle have complicated the description of mechanisms that maintain and regulate cardiac cell volume. The objective of the proposed research is to describe specific sarcolemmal transport pathways involved in cardiac cell volume homeostasis and to determine which signal transduction mechanisms are involved in the activation of these transport pathways. Embryonic chick heart cells cultured as isolated cells or grown to confluency in linear or spherical geometries will be used to evaluate the role of cations, anions, and osmolytes in the maintenance of cardiac cell volume. Swelling-activated (both isosmotic and hyposmotic) transport pathways will be identified and characterized using voltage/patch clamp, ion-selective microelectrodes, microspectrofluorimetry, video microscopy and cell biochemistry. Signal transduction mechanisms activated by cell swelling will be identified and the effects of activation/inhibition of specific transduction mechanisms on swelling-activated transport will be assessed. These studies will define fundamental principles of cardiac cell volume regulation; such principles will provide the foundation for studies of the pathophysiological changes in cell volume associated with myocardial ischemia, congestive heart failure and cardioplegia.
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