Our research project focuses on the study of unresolved problems of the mechanisms of ion transport across the apical and basolateral membranes of defined tubule segments. We shall apply tubule perfusion and patch- clamp techniques to evaluate cellular and molecular transport mechanisms of Na,K,C1 and H and their physiological regulation. First, we propose to explore the mechanism of proximal tubule chloride transport with emphasis o apical formate-chloride and oxalate-chloride exchange. These studies will be directed at the nature of the recycling mechanisms of formate and oxalate and the participation of the anion exchangers in the physiological regulation of proximal tubule NaCI transport. We shall also investigate the role of chloride channels in the basolateral membrane in mediating net chloride reabsorption. Second, we propose to study the interaction of Na,K,Ca and H transport in principal tubule cells. We shall analyse their acid-base transport mechanisms, and explore their regulation and interaction with net sodium and potassium transport. Our studies will provide insights into "membrane cross-talk" and the signaling pathways affecting Na,K,pH and Ca homeostasis. Third, we propose to explore the apical low-conductance K channel in principal tubule cells. We shall address unresolved problems of conduction mechanism and physiological regulation. We also plan to explore a recently clone ATP-sensitive channel and compare its properties with native K channels in principal tubule cells.