The proposed research focuses on cardiac cell volume regulation, and studies will be carried out on freshly isolated single rabbit ventricular cells. Cardiac cell edema is well recognized in the setting of ischemia and congestive heart failure. Defects in cell volume regulation are associated with cellular damage as well as contractile and electrical dysfunction. Preliminary studies suggest that stretch-activated (SA) cation and anion channels may contribute to cardiac cell volume regulation. The candidate will utilize the patch clamp and ion selective microelectrode techniques to characterize the properties and regulation of SA cation and anion channels at the single channel level, and their contribution to membrane currents and intracellular ion activities of K+, Na+, and C1-. The combination of these electrophysiological measurements and cell volume determinations will provide new information about basic mechanisms of cell volume regulation. Further, the hypothesis that cytoskeletal elements and cyclic nucleotides modulate SA channels in heart will be tested. A better understanding of basic mechanisms of cell volume regulation is a precursor to developing strategies to minimize cellular damage during ischemia and congestive failure.
