Electroneutral uptake and electrogenic secretion of a fluorescent bile salt by rat hepatocyte couplets

Am J Physiol. 1993 Feb;264(2 Pt 1):G220-30. doi: 10.1152/ajpgi.1993.264.2.G220.

Abstract

The role of membrane voltage as a driving force for the hepatic uptake and secretion of fluorescent bile salts has been examined in isolated hepatocyte couplets. The present study demonstrates that the fluorescent bile salt derivative (N-[7-(nitrobenz-2-oxa- 1,3-diazol-4-yl)]-7-amino-3 alpha, 12 alpha-dihydroxy-5-cholan-24-oyl)-2-aminoethanesulfonate (7 beta-NBD-NCT) is taken up into hepatocytes by a saturable process with a Kt of 2.7 microM. Uptake rate was reduced by only 22% after total Na+ replacement and was independent of transmembrane potential difference over a range of -135 to +25 mV. In contrast, secretion into the canalicular space was strongly dependent on membrane voltage over the range from -34 to 0 mV in a manner consistent with electrodiffusion of an anion. Fitting the secretion time course to that predicted by electrodiffusion demonstrated that only approximately 50% of total secretion can result from electrodiffusion. Studies in isolated perfused liver confirmed this observation that depolarization caused a decrease in bile salt secretion rate. These results demonstrate that 7 beta-NBD-NCT is transported by a neutral uptake process at the sinusoidal membrane and is secreted across the canalicular membrane in part by electrogenic transport. This suggests that voltage changes could be a common pathway resulting in impaired organic anion secretion in diverse cholestatic syndromes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism*
  • Biological Transport / drug effects
  • Electrochemistry
  • Electrophysiology
  • Ions
  • Liver / cytology
  • Liver / metabolism*
  • Liver / physiology
  • Microscopy, Fluorescence
  • Oxadiazoles / pharmacokinetics*
  • Perfusion
  • Potassium / pharmacology
  • Rats
  • Taurine / analogs & derivatives*
  • Taurine / pharmacokinetics
  • Taurocholic Acid / metabolism

Substances

  • Bile Acids and Salts
  • Ions
  • Oxadiazoles
  • (N-(7-(nitrobenz-2-oxa-1,3-diazol-4-yl))-7-amino-3alpha,12alpha-dihydroxycholan-24-oyl)-2-aminoethanesulfonate
  • Taurine
  • Taurocholic Acid
  • Potassium