HCO 3 − -coupled Na+ influx is a major determinant of Na+ turnover and Na+/K+ pump activity in rat hepatocytes

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Abstract
Recent studies in hepatocytes indicate that Na+-coupled HCO 3 − transport contributes importantly, to regulation of intracellular pH and membrane HCO 3 − transport. However, the direction of net coupled Na+ and HCO 3 − movement and the effect of HCO 3 − on Na+ turnover and Na+/K+ pump activity are not known. In these studies, the effect of HCO 3 − on Na+ influx and turnover were measured in primary rat hepatocyte cultures with22Na+, and [Na+] i was measured in single hepatocytes using the Na+-sensitive fluorochrome SBFI. Na+/K+ pump activity was measured in intact perfused rat liver and hepatocyte monolayers as Na+-dependent or ouabain-suppressible86Rb uptake, and was measured in single hepatocytes as the effect of transient pump inhibition by removal of extracellular K+ on membrane potential difference (PD) and [Na+] i . In hepatocyte monolayers, HCO 3 − increased22Na+ entry and turnover rates by 50–65%, without measurably altering22Na+ pool size or cell volume, and HCO 3 − also increased Na+/K+ pump activity by 70%. In single cells, exposure to HCO 3 − produced an abrupt and sustained rise in [Na+] i , from ≈8 to 12mm. Na+/K+ pump activity assessed in single cells by PD excursions during transient K+ removal increased ≃2.5-fold in the presence of HCO 3 − , and the rise in [Na+] i produced by inhibition of the Na+/K+ pump was similarly increased ≃2.5-fold in the presence of HCO 3 − . In intact perfused rat liver, HCO 3 − increased both Na+/K+ pump activity and O2 consumption. These findings indicate that, in hepatocytes, net coupled Na+ and HCO 3 − movement is inward and represents a major determinant of Na+ influx and Na+/K+ pump activity. About half of hepatic Na+/K+ pump activity appears dedicated to recycling Na+ entering in conjunction with HCO 3 − to maintain [Na+] i within the physiologic range.