Evidence for norepinephrine-activated Ca2+ permeable channels in guinea-pig hepatocytes using a patch clamp technique.

To determine whether the hepatocyte plasma membrane possesses a Ca2+ channel. we applied a patch clamp technique to isolated guinea-pig hepatocytes. In a cell-attached configuration, using an internal pipette solution of 110 mM BaCl2 or CaCl2, we observed sporadic inward single channel currents (Po = 0.004 +/- 0.002, n = 6) at various membrane potentials. The unit amplitude was 0.60 +/- 0.15 pA (n = 6) at resting membrane potential. The single channel conductance was 20.4 +/- 4.6 pS (n = 6) and this channel showed no rectification and no voltage dependence. Bay K 8644, a dihydropyridine Ca2+ channel activator, did not affect this channel activity. Although norepinephrine in the pipette solution did not activate this channel, its external application increased channel activity. These observations suggest that guinea-pig hepatocytes possess Ca2+ permeable channels that differ from the voltage-operated Ca2+ channels found in excitable cells and that such channels are responsible for the agonist-stimulated Ca2+ entry in hepatocytes.