Uptake of bromosulfophthalein via SO2-4/OH- exchange increases the K+ conductance of rat hepatocytes.
In confluent primary cultures of rat hepatocytes, micromolar concentrations of bromosulfophthalein (BSP) lead to a sizeable hyperpolarization of membrane voltage. The effect is a saturable function of BSP concentration yielding an apparent value of 226 micromol/l and a Vmax of -10.3 mV. The BSP-induced membrane hyperpolarization is inhibited by the K+ channel blocker Ba2+, and in cable-analysis and ion-substitution experiments it becomes evident that the effect is due to a significant increase in cell membrane K+ conductance. Voltage changes were attenuated by the simultaneous administration of SO2-4, succinate, and cholate (cis-inhibition) and increased after preincubation with SO2-4 and succinate (trans-stimulation), suggesting that the effect occurs via BSP uptake through the known SO2-4/OH- exchanger. Microfluorometric measurements reveal that BSP-induced activation of K+ conductance is not mediated by changes in cell pH, cell Ca2+, or cell volume. It is concluded that K+ channel activation by BSP (as well as by DIDS and indocyanine green) may reflect a physiological mechanism linking the sinusoidal uptake of certain anions to their electrogenic canalicular secretion.
Wehner
F
F
Max-Planck-Institut für molekulare Physiologie, Abteilung Epithelphysiologie, 44139 Dortmund, Germany. frank.wehner@mpi-dortmund.mpg.de
Tinel
H
H
D000818:Animals; D002478:Cells, Cultured; D020355:Cholates / Q000494:pharmacology; D004338:Drug Combinations; D004553:Electric Conductivity; D017665:Hydroxyl Radical / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D051381:Rats; D013386:Succinates / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism* / Q000494:pharmacology; D013448:Sulfobromophthalein / Q000493:pharmacokinetics*
D020355:Cholates; D004338:Drug Combinations; D013386:Succinates; D013431:Sulfates; D013448:Sulfobromophthalein; D017665:Hydroxyl Radical; D011188:Potassium