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

Abstract

Recent studies in hepatocytes indicate that Na(+)-coupled HCO3- transport contributes importantly to regulation of intracellular pH and membrane HCO3- transport. However, the direction of net coupled Na+ and HCO3- movement and the effect of HCO3- on Na+ turnover and Na+/K+ pump activity are not known. In these studies, the effect of HCO3- on Na+ influx and turnover were measured in primary rat hepatocyte cultures with 22Na+, 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-suppressible 86Rb 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, HCO3- increased 22Na+ entry and turnover rates by 50-65%, without measurably altering 22Na+ pool size or cell volume, and HCO3- also increased Na+/K+ pump activity by 70%. In single cells, exposure to HCO3- produced an abrupt and sustained rise in [Na+]i from approximately 8 to 12 mM. Na+/K+ pump activity assessed in single cells by PD excursions during transient K+ removal increased congruent to 2.5-fold in the presence of HCO3-, and the rise in [Na+]i produced by inhibition of the Na+/K+ pump was similarly increased congruent to 2.5-fold in the presence of HCO3-. In intact perfused rat liver, HCO3- increased both Na+/K+ pump activity and O2 consumption. These findings indicate that, in hepatocytes, net coupled Na+ and HCO3- 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 HCO3- to maintain [Na+]i within the physiologic range.

Modular structure of sodium-coupled bicarbonate transporters

“…basolateral) membrane of hepatocytes , where electrogenic Na/HCO 3 cotransport (Fitz et al, 1991b;Renner et al, 1989) is a major contributor to Na + and HCO 3 -influx under basal conditions (Fitz et al, 1989;Fitz et al, 1991a;Fitz et al, 1991b). This influx influences such hepatic functions as urea synthesis and gluconeogenesis (Kashiwagura et al, 1984).…”

Activation of protein kinase C? couples cell volume to membrane Cl? permeability in HTC hepatoma and Mz-ChA-1 cholangiocarcinoma cells

“…Previous studies indicate that hormonal control of metabolic function requires selective modulation of membrane ion permeability, which changes of 10-to 50-fold following receptor stimulation. [1][2][3][4][5] However, because differences in transmembrane osmolarity as low as 1 mosmol · kg Ϫ1 are sufficient to produce rapid changes in water movement, 6 solute uptake and efflux rates must be carefully balanced to minimize associated changes in cell volume. 7 While these general principles are relevant to all cells, regulation of liver cell volume is particularly demanding, because dual perfusion from the systemic and portal circulations subjects liver cells to substantial changes in nutrient supply, hormones, and oxidative stress between the fed and fasted states.…”

Volume-sensitive Tyrosine Kinases Regulate Liver Cell Volume through Effects on Vesicular Trafficking and Membrane Na+ Permeability

“…the hepatocyte plasma membrane is low under basal conditions and is balanced by an equivalent rate of Na ϩ efflux through Na ϩ /K ϩ pump activity to maintain intracellular [Na ϩ ] near 8 mM (38). Decreases in cell volume are followed after a delay by an increase in Na ϩ influx mediated by (i) a Na ϩ -permeable channel, (ii) Na ϩ /H ϩ exchange, and (iii) Na ϩ /K ϩ /2Cl Ϫ cotransport (7).…”