Bile acid uptake via the human apical sodium-bile acid cotransporter is electrogenic.
Intestinal absorption of bile acids depends on a sodium-bile acid cotransport protein in the apical membrane of the ileal epithelial cell. Transport is Na+-dependent, but the Na+-bile acid stoichiometry and electrogenicity of transport are not known. Studies in whole intestine, isolated cells, and ileal membrane vesicles have been unable to resolve this issue because transport currents are small and can be obscured by other ionic conductances and transport proteins present in these membranes. In this study, the human apical sodium-bile acid transporter was expressed in stably transfected Chinese hamster ovary cells that lack other bile acid transporters. The Na+-dependent transport of a fluorescent bile acid analog, chenodeoxycholyl-Nepsilon-nitrobenzoxadiazol-lysine, was monitored by fluorescence microscopy in single, voltage-clamped cells. Bile acid movement was bidirectional and voltage-dependent with negative intracellular voltage-stimulating influx. A 3-fold reduction in extracellular Na+ produced a negative 52 mV shift of the flux-voltage relationship, consistent with a 2:1 Na+:bile acid coupling stoichiometry. No Na+- or voltage-dependent uptake was observed in nontransfected Chinese hamster ovary cells. These results indicate that the cotransport of bile acids and Na+ by human apical sodium-bile acid transporter is electrogenic and bidirectional and is best explained by a 2:1 Na+:bile acid coupling stoichiometry. These results suggest that membrane potential may regulate bile acid transport rates under physiological and pathophysiological conditions.
Weinman
S A
SA
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, USA. sweinman@utmb.edu
Carruth
M W
MW
Dawson
P A
PA
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D002793:Cholic Acids / Q000378:metabolism; D006224:Cricetinae; D004553:Electric Conductivity; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D027981:Symporters; D013656:Taurocholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D002793:Cholic Acids; D029363:Organic Anion Transporters, Sodium-Dependent; D011994:Recombinant Proteins; D027981:Symporters; C095008:cholyl-nitrobenzoxadiazolyl-lysine; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid; D012964:Sodium; D008239:Lysine