Hyperpolarization by Noradrenaline in Guinea pig Liver Cells: Effbcts of Ouabain and External Ca2+

The mechanism of hyperpolarization of the membrane caused by noradrenaline (NA) was investigated in guinea pig liver cells. The hyperpolarization produced by NA was accompanied by a reduction of membrane resistance. Both hyperpolarization and reduction of membrane resistance were suppressed by ouabain (5 x 10(-6) M). However, when the external Na+ was reduced to 38 mM, the NA response reappeared even in the presence of ouabain. The hyperpolarizing NA response may be divided into two phases, an early phase and a late phase. In a Ca2+-free solution, the NA response gradually disappeared. However, the early phase of hyperpolarizing response was more resistant to a removal of external Ca2+ than the late phase. Manganese ion also suppressed the late phase more strongly than the early phase. It was concluded that the hyperpolarization induced by noradrenaline is due to an increase in K+ conductance and that this may be a result of an increase in intracellular Ca2+ concentration. The early phase of hyperpolarizing NA response is probably due to release of bound Ca2+ and the late phase to influx of Ca2+ from the external solution. Suppression of the NA response by ouabain may be explained by assuming that the Ca2+- activated K+ conductance is blocked by an increase in intracellular Na+ concentration.