Forskolin-induced block of delayed rectifying K+ channels in pancreatic beta-cells is not mediated by cAMP.

K+ channels in the membrane of murine pancreatic beta-cells were studied using the patch-clamp technique. The delayed outward current was activated in whole-cell experiments by depolarizing voltage pulses to potentials between -30 mV and 0 mV. Forskolin blocked the current rapidly (less than 5 s) and reversibly with 50% inhibition at 13 microM. The inhibition did not depend on a stimulation of the adenylate cyclase since it occurred even in presence of 1 mM cAMP in the pipette solution which replaced the cytoplasm. Membrane permeant cAMP analogues and phosphodiesterase inhibitors did not influence the delayed outward current. In experiments on outside-out patches forskolin (100 microM) shortened the openings of a channel of about 10 pS conductance at 0 mV and a time course of activation and inactivation similar to the whole-cell current. Another smaller, slowly activating channel and the Ca2+- and ATP-dependent K+ channels were influenced only weakly or not at all. It is therefore concluded that the 10-pS channel generates most of the delayed outward K+ current in murine pancreatic beta-cells. The Ca2+-independent part of the delayed outward current in bovine adrenal chromaffin cells was also blocked by forskolin (100 microM).