Evidence for bile acid-evoked oscillations of Ca2(+)-dependent K+ permeability unrelated to a D-myo-inositol 1,4,5-trisphosphate effect in isolated guinea pig liver cells.
In single liver cells, the D-myo-inositol 1,4,5-triphosphate (InsP3)-dependent agonists such as noradrenaline and angiotensin II evoke oscillations in intracellular calcium [Ca2+]i resulting mostly from the periodic release and reuptake of calcium from intracellular stores. In the present work, we have reexamined the effects of these agonists and investigated whether the natural bile acid taurolithocholic acid 3-sulfate (TLC-S), which permeabilizes the endoplasmic reticulum, could initiate oscillations of [Ca2+]i. Oscillations of [Ca2+]i were monitored with the Ca2(+)-dependent K+ permeability in whole-cell voltage-clamped guinea pig liver cells. Our results confirm the presence of two types of oscillations induced by hormones. They could be distinguished by their frequency periods. The fast (type I) had periods ranging from 5 to 12 s and the slow (type II) from 60 to 240 s. They have been respectively attributed to second messenger- and receptor-controlled oscillations, respectively. Our results also show that TLC-S, as noradrenaline and angiotensin II, induced the activation of this Ca(+)-dependent K+ current and was able to reproduce both types of oscillations. The bile acid effect was not blocked by intracellular perfusion of heparin known to inhibit both InsP3 binding and InsP3-evoked Ca2+ release in several tissues. In these conditions, TLC-S only evoked type I oscillations, suggesting that these fluctuations could originate from a mechanism that is independent of InsP3 and is an intrinsic property of internal Ca2+ stores.
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Institut National de la Santé et de la Recherche Médicale, Unité 274, Université Paris-Sud, Orsay, France.
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012503:Saponins / Q000494:pharmacology; D013658:Taurolithocholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D015221:Potassium Channels; D012503:Saponins; D000804:Angiotensin II; C066776:taurolithocholic acid 3-sulfate; D013658:Taurolithocholic Acid; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine