Ions and Cellular Homeostasis

There are three areas of research in the lab all of which focus on receptor mediated regulation of plasma membrane transporters. They are briefly described below. I. Ionic Homeostasis in Hypovolemia: Renal Mechanisms The overall objective of this project is to elucidate the renal mechanisms in the intercalated cells of the cortical collecting duct involved in the adaptation to hypovolemia as may occur in such conditions as diarrhea, diuretic use, and congestive heart failure. K -sparing is an important homeostatic component in response to hypovolemia but the means by which K is conserved when NaCl is reabsorbed in the cortical collecting duct is not understood. We are testing the hypothesis that the intercalated cells of the cortical collecting duct are responsible for K reabsorption and is effected by two H -K -ATPase enzymes localized to the luminal side of the intercalated cells. The mechanism by which Cl- reabsorption accompanies Na reabsorption from lumen to blood is also being examined by investigating the role of an apical Cl-/HCO-3 exchanger found in the base secreting intercalated cell sub-type. It is predicted that the net effect of these processes is to ensure that K sparing, and acid-base homeostasis accompanies NaCl reabsorption. Furthermore, it is believed that angiotensin is the hormone responsible for mediating the chronic effects of volume depletion on H -K -ATPase activity and apical Cl-/HCO3- exchanger activity via AT1A receptor activation. The overall premise for conducting these experiments is that if we understand the physiological basis by which the body normally conserves K then we will also have identified a target that potentially can be exploited for therapy of disorders of K metabolism. II. Histamine H3-Receptors in Cardiac Sympathetic Nerve Endings: Role in Norepinephrine Release