The proposal will test the hypothesis that membrane conductance is regulated through the mediation of intracellular messengers, and that this regulation secondarily affects both the cell membrane potential and electrogenic membrane transport processes. Specifically, this application will assess the role of the adenylate cyclase/cAMP mediated messenger pathway and the inositol phospholipid messenger pathway in regulating membrane conductances and membrane transport in brush border and basolateral membrane vesicles of rat renal proximal tubule. Additionally, this proposal will determine whether hormonally induced changes in these messenger pathways result in changes in permeability, ionic conductances and transport in isolated convoluted and straight segments of proximal tubules, and in membrane vesicles derived from these heterogeneous nephron sites. To accomplish these goals, membrane permeabilities and conductances will be evaluated with the fluorescent and isotopic assays that have been developed in this laboratory, and transport will be examined utilizing specific substrates that are electrogenically transported in either the brush border or basolateral membranes.
