Intracellular chloride activity in the intact rat liver: Relationship to membrane potential and bile flow

Active chloride transport has been described in a variety of epithelia, and intracellular chloride activity a(Cl)(i) in these tissues is generally elevated twofold or more above the level predicted for passive diffusion. To determine whether active chloride transport might contribute to canalicular bile formation, we have used conventional and Cl^--selective microelectrodes to measure a(Cl)(i) of rat hepatocytes in vivo under a variety of conditions. Under basal conditions, the membrane potential difference averaged -33.2 ± 3.5 mV (means ± SD) in 29 animals, and the ratio (R) of observed a(Cl)(i) (24.8 mM) to that expected for passive distribution at this membrane potential (22.6 mM) was 1.10 ± 0.08, a value slightly but significantly greater than that predicted for passive distribution. Infusion of alanine (45-μmol bolus, 10.8-μmol/min infusion) in 5 animals hyperpolarized the membrane potential to -43.6 ± 4.0 mV over 10-15 min and resulted in a significant fall in a(Cl)(i) to 15.1 ± 4.8 mM but with no change in R. Infusion of theophylline (577 nmol/min), taurocholate (3-μmol bolus, 810-nmol/min infusion), and ursodeoxycholic acid (4-μmol bolus, 2.13-μmol/min infusion) into 5 animals each increased bile flow by 6.1, 34.1, and 96.8%, respectively, compared with saline-infused controls but did not alter membrane potential or chloride distribution. These observations indicate that a(Cl)(i) is close to the level predicted for passive distribution under basal conditions, after hyperpolarization of the membrane potential by alanine, and after stimulation of bile flow by a variety of choleretics. By analogy with Cl^--secreting epithelia, it appears unlikely that active chloride transport across the basolateral membrane contributes significantly to canalicular bile formation by the hepatocyte.