Department of Clinical Science
We study the function and regulation of Na transporters in the surface membrane of mammalian cells, recently with a focus on the regulation of transporters by surface membrane turnover via exo- and endocytosis. To so do, we employ innovative electrical and optical methods. Three Na transporters have been of most interest to us; Na/Ca exchangers, Na/K pumps, and Na/H exchangers, all of which can determine the fate of cardiac cells in pathological settings such as ischemia. To improve biophysical and regulatory studies of these mechanisms, we developed 'giant' patch clamp methods and analyzed conformational changes of transport proteins with 1 microsecond resolution. Recently, we refined ion selective electrode methods to measure ion fluxes independent of electrical activity. Along the way, we discovered that phosphatidylinositides are powerful direct regulators of ion transporters and channels. We are now studying nonconventional endocytic processes that become highly activated in response to metabolic stress. We recently disovered that these domain-driven endocytic processes become activated during ischemia/reperfusion of the heart and can rapidly internalize >30% of the sarcolemma. These studies open new pathways to understand dynamics of cell membranes that are highly relevant to states disease that involve metabolic stress.
Biochemical mechanisms of autophagy,DNA damage and HDACi induced apoptosis,Primary ciliogenesis,Regulated necrosis