Role of extracellular Ca2+ in hepatic bile formation and taurocholate transport

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Abstract
The role of extracellular Ca2+ in hepatic bile formation, biliary membrane permeability, and taurocholate (TC) transport was studied in isolated perfused rat livers and in isolated rat hepatocytes to determine the functional importance of paracellular permeability in biliary bile acid excretion. Each liver was perfused for 1 h with perfusate containing 1.3 mM Ca2+ (control period) followed by another hour with 1.3, 0.5, 0.1, 0.05, 0.03, or 0.01 mM Ca2+ (experimental period). Basal bile flow and biliary excretion of added TC declined significantly only at and below 0.05 mM perfusate Ca2+ and was associated with an increase in bile-to-perfusate concentration ratio of [3H]inulin (B/P inulin ratio). A twofold increase in the diffusional permeability coefficient at 0.05 mM and a sixfold increase at 0.03 and 0.01 mM perfusate Ca2+ could explain the increased in B/P inulin ratios. Time-dependent increases in cell-to-medium concentration ratios of inulin were less in the absence than in the presence of Ca2+. Hepatic uptake rates of TC determined in isolated hepatocytes and from perfusate disappearance of added TC and efflux rates of TC from preloaded hepatocytes were not significantly affected by Ca2+ removal. It is possible that the observed decline in biliary TC excretion at low perfusate Ca2+ is due to regurgitation of secreted TC back into the perfusate followed by reuptake. This was supported by an accumulation of perfusate radioactivity when TC uptake inhibitors (furosemide and bumetanide) were added to the perfusate (0.03 mM Ca2+) 60 min after the addition of [14C]TC.(ABSTRACT TRUNCATED AT 250 WORDS)