Department of Medicine, University of Cincinnati, and the Veterans Affairs Medical Center, Cincinnati, Ohio, USA

Correspondence: Manoocher Soleimani, M.D., Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati, 231 Bethesda Avenue, MSB 5502, Cincinnati, Ohio 45267–0585, USA. E-mail: Manoocher.Soleimani@uc.edu

Received 16 April 1999; Revised 28 June 1999; Accepted 21 July 1999.

Abstract

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 proximal tubule via a process of active acid secretion by the luminal membrane. The major mechanism for the transport of HCO₃^- across the basolateral membrane is via the electrogenic Na⁺:3HCO₃^- cotransporter (NBC). Recent molecular cloning experiments have identified the existence of three NBC isoforms (NBC-1, NBC-2, and NBC-3).¹ Functional and molecular studies indicate the presence of all three NBC isoforms in the kidney. All are presumed to mediate the cotransport of Na⁺ and HCO₃^- under normal conditions and may be functionally altered in certain pathophysiologic states. Specifically, NBC-1 may be up-regulated in metabolic acidosis and potassium depletion and in response to glucocorticoid excess and may be down-regulated in response to HCO₃^- loading or alkalosis. Recent studies provide molecular evidence indicating the expression of NBC-1 in pancreatic duct cells. NBC is activated by cystic fibrosis transmembrane conductance regulator (CFTR) and plays an important role in HCO₃^- secretion in the agonist-stimulated state in pancreatic duct cells. The purpose of this review is to summarize recent functional and molecular studies on the regulation of NBCs in physiologic and pathophysiologic states. Possible signals responsible for the regulation of NBCs in these conditions are examined. Furthermore, the possible role of this transporter in acid-base disorders (such as proximal renal tubular acidosis) is discussed.