Regulation of hepatic Na⁺-HCO₃/^- cotransport and pH by membrane potential difference

Hepatocytes possess several mechanisms for membrane acid-base transport, which work in concert to maintain intracellular pH (pH(i)) in a narrow physiological range, despite metabolic processes that produce and consume substantial quantities of H⁺ and HCO₃/^-, Na⁺-H⁺ and Cl^--HCO₃/^- exchangers contribute to recovery from intracellular acidosis and alkalosis, respectively, but are largely inoperative at physiological values of pH(i). Recent studies indicate that hepatocytes also possess a mechanism for coupled transport of Na⁺ and HCO₃/^- across the basolateral membrane. This appears to be the dominant pathway for membrane acid-base transport operative under basal conditions, mediates influx of Na⁺ and HCO₃/^-, and is an important contributor to recovery from intracellular acidosis. In this review, the properties of hepatic Na⁺-HCO₃/^- cotransport are described with emphasis on its effects on pH(i) and Na⁺ homeostasis and on the possible role of membrane potential difference as a signal modulating the rate of HCO₃/^- influx and pH(i) of hepatocytes through effects on this transporter.