Chloride transport by intact rat liver and cultured rat hepatocytes.

Chloride is the predominant inorganic anion in bile, and it has been proposed that active chloride transport, possibly via a sodium-coupled mechanism, may contribute to that portion of canalicular bile formation not directly related to bile acid transport (bile acid-dependent bile formation or BAIBF). We have therefore examined the anion specificity of BAIBF using the isolated perfused rat liver and have studied sodium-chloride flux coupling and the sodium dependence of intracellular chloride content using 22Na and 36Cl transport by cultured rat hepatocytes. BAIBF by the isolated rat liver was unaltered by replacement of chloride with nitrate or benzenesulfonate but was significantly reduced by replacement of chloride with sulfate or thiocyanate. In cultured hepatocytes, sodium entry rate was reduced when chloride in the incubation medium was replaced by cyclamate, benzenesulfonate, or sulfate and mannitol but was unaffected when chloride was replaced by nitrate, gluconate, or thiocyanate. Conversely, chloride entry rate was decreased when sodium was replaced with choline but was unaffected when sodium was replaced by lithium or when ouabain was added to the medium. Thus no consistent evidence of sodium-chloride flux coupling was observed. Steady-state exchangeable intracellular chloride in the cultured hepatocytes was unaffected by ouabain or by replacement of sodium with choline and was increased when sodium was replaced by lithium. These findings indicate that basal BAIBF exhibits no specific chloride requirement. Although they do not exclude the possible existence in rat liver of sodium-coupled chloride transport, they provide no evidence that such a mechanism accounts for a major portion either of chloride transport by individual rat hepatocytes or of basal BAIBF by intact rat liver.