Internal perfusion of guinea-pig hepatocytes with buffered Ca2+ or inositol 1,4,5-trisphosphate mimics noradrenaline activation of K+ and Cl- conductances.
External application of noradrenaline to voltage-clamped guinea-pig isolated hepatocytes evoked membrane conductance increases to K+ and Cl-. This effect was reproduced by internal perfusion of the cells with 2 microM buffered Ca2+ and with 20 microM inositol 1,4,5-trisphosphate (IP3). The kinetic properties of the K+ conductance and its selective block by the toxin apamin were the same in each case. Cyclical fluctuations of conductance observed with noradrenaline were reproduced by internal IP3 but not by Ca2+ perfusion, indicating that oscillations of intracellular free Ca2+ may arise from properties of the Ca2+ sequestration mechanism at constant IP3 concentration.
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D006168:Guinea Pigs; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits; D013403:Sugar Phosphates / Q000494:pharmacology*
D002712:Chlorides; D007295:Inositol Phosphates; D007473:Ion Channels; D013403:Sugar Phosphates; D001030:Apamin; D015544:Inositol 1,4,5-Trisphosphate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine