REGULATORY MECHANISMS INVOLVED IN THE ACTIVATION OF BRADYKININ-INDUCED MEMBRANE CURRENTS IN PC12 CELLS

Whole-cell patch-clamp measurements were made in nerve-growth-factor (NGF)-treated PC12 cells. External application of bradykinin (BK) activated an outward and an inward current which could be separated by using KCl- or CsCl-containing pipette solutions. The slowly activating inward current could be induced by BK independently of the filling of intracellular Ca2+ stores. By using GDP-beta-S in the pipette medium, we showed that BK-induced outward and inward currents were differentially regulated through G-protein-sensitive and -insensitive mechanisms, respectively. While the outward current was inhibited by GDP-beta-S, the inward current was not affected. Our results show that occupancy of BK receptors activates different signaling pathways for the induction of outward and inward currents.