Physiologic and molecular aspects of the Na+: HCO3- cotransporter in health and disease processes

Approximately 80% of the filtered load of HCO3- is reabsorbed in the proxim al tubule via a process of active acid secretion by the luminal membrane. T he major mechanism for the transport of HCO3- across the basolateral membra ne is via the electrogenic Na+:3HCO(3)(-) cotransporter (NBC). Recent molec ular cloning experiments have identified the existence of three NBC isoform s (NBC-1, NBC-2, and NBC-3).(1) Functional and molecular studies indicate t he presence of all three NBC isoforms in the kidney. All are presumed to me diate the cotransport of Na+ and HCO3- under normal conditions and may be f unctionally altered in certain pathophysiologic states. Specifically, NBC-1 may be up-regulated in metabolic acidosis and potassium depletion and in r esponse to glucocorticoid excess and may be down-regulated in response to H CO3- loading or alkalosis. Recent studies provide molecular evidence indica ting the expression of NBC-1 in pancreatic duct cells. NBC is activated by cystic fibrosis transmembrane conductance regulator (CFTR) and plays an imp ortant role in HCO3- secretion in the agonist-stimulated state in pancreati c duct cells. The purpose of this review is to summarize recent functional and molecular studies on the regulation of NBCs in physiologic and pathophy siologic states. Possible signals responsible for the regulation of NBCs in these conditions are examined. Furthermore, the possible role of this tran sporter in acid-base disorders (such as proximal renal tubular acidosis) is discussed.