| Abstract: | We have investigated the effects of glucagon and forskolin upon pancreatic islet cell electrical activity using intracellular recordings from single mouse islets. Glucagon (0.1-2.0 microM) and forskolin (0.5-5.0 microM), both adenylate cyclase activators, potentiated glucose (200 mg/dl)-induced electrical activity. In the steady-state, islet cells have cyclic electrical activity with periodically recurring "plateau" depolarizations (with superimposed Ca++ action potentials) separated by silent hyperpolarizations. Both glucagon and forskolin mimicked glucose stimulation by increasing the fraction of each cycle spent in the plateau phase (the "plateau fraction"). Unlike glucose, however, glucagon and forskolin increased, rather than decreased, the overall frequency of plateaus, suggesting that plateau frequency is not tightly linked to changes of plateau fraction. This dissociation was also apparent during the onset of drug action. Plateau fraction increased immediately (within one minute), fell to a nadir and then rose to a new steady state level. Plateau frequency, however, rose slowly and monotonically to a new level. Following drug withdrawal plateau fraction returned to control levels several minutes before plateau fraction. From these results it was concluded that cAMP has two effects upon islet cell electrical activity: one is to increase plateau fraction possibly by stimulating glucose-dependent process, which results in increasing in Ca++ influx, and the other to increase plateau frequency possibly by reducing intracellular Ca++ buffering. |
