Renal H,K-ATPase: structure, function and regulation.

The H,K-ATPase comprises a family of isoenzymes with unique biochemical, pharmacological, and regulatory properties. This review explores recent advances in discovery of the molecular biology, biochemistry, and function of these ion pumps, with particular emphasis on the implications for renal potassium and proton handling. Structure-function correlations governing the ion transport mechanisms, inhibitor binding sites, oligomerization, and transcriptional control of the H,K-ATPase isoforms are examined. Functional studies of H,K-ATPase in renal tubules and cultured epithelial cells are analyzed and related to data concerning the expression and distribution of the H,K-ATPase gene products in the kidney. Functional and molecular biological evidence for adaptive changes in renal H,K-ATPase expression during the evolution of potassium and acid-base disturbances are discussed. Current investigative challenges and avenues for future research of these enzymes are presented.