Models of depressed hepatic mrp2 activity reveal bromosulphophthalein-sensitive passive K+ flux.
Bile acid independent flow composes up to 40% of hepatic bile secretory capacity. Apical (canalicular) efflux of non-bile-acid organic anions provides the major osmotic driving force for bile acid independent flow. Organic anion accumulation in the hepatocyte is accompanied by increases in both K+ conductance in isolated hepatocytes and passive K+ flux in the perfused rat liver, which are indicative of K+ channel activation. We used two models of disrupted canalicular anion transport to test whether organic anion stimulated K+ efflux occurs independently of anion excretion. In both wild type (wt) and mrp2 mutant (transport minus, tr-) rat liver, bromosulfophthalein (BSP; 0.5 mM) caused a reversible increase in K+ flux that (i) was outwardly directed with low external K+ and (ii) depended upon the electrochemical potential for K+. K+ efflux from wt livers of both sexes was about 1.5 times larger than that from tr- livers. Further, K+ release from female rat livers was about three times higher than that from male livers, independent of phenotype. Two transcripts of the rat hepatocyte K+ channel (Kir4.2) were expressed in hepatocytes of all rats. The results demonstrate that BSP stimulates basolateral (sinusoidal) K+ channels independently of its canalicular excretion, revealing an early event in BAIF and suggesting that Kir4.2 may mediate BSP-sensitive K+ flux.
Li
Qin
Q
Gastrointestinal Diseases Research Unit and Department of Physiology, Queen's University, Kingston, ON K7L 3N6, Canada.
Briggs
M Martha
MM
Folkens
Doris
D
Hill
Ceredwyn E
CE
D000818:Animals; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012269:Ribosomal Proteins / Q000172:deficiency* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013448:Sulfobromophthalein / Q000494:pharmacology*
C093947:MRP2 protein, S cerevisiae; D024101:Mitochondrial Proteins; D015221:Potassium Channels; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D013448:Sulfobromophthalein