Forskolin, an activator of adenylate cyclase, increases CA2+-dependent electrical activity induced by glucose in mouse pancreatic B cells.

The effects of forskolin, an activator of adenylate cyclase, on the membrane potential of pancreatic B cells have been studied with microelectrodes. Forskolin (5 microM) did not affect the stable resting membrane potential (3 mM glucose). In the presence of 10 mM glucose, forskolin lengthened the slow waves with superimposed spikes and shortened the polarized intervals between them. This caused a marked increase in the frequency of the slow waves and doubled the fraction of time spent at a depolarized level, with spike activity. The frequency of the spikes was not changed. The effects of forskolin were of rapid onset, but were only slowly and partially reversible; they were completely blocked when Ca2+ influx was prevented by cobalt. The results show that forskolin increases electrical events underlain by Ca inward currents and suggest that, besides its action on intracellular Ca stores, cyclic AMP could also modulate the permeability of Ca channels in the plasma membrane of B cells.