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).
Zünkler
B J
BJ
Max-Planck-Institut für biophysikalische Chemie, Göttingen, Federal Republic of Germany.
Trube
G
G
Ohno-Shosaku
T
T
D000818:Animals; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011188:Potassium / Q000378:metabolism*
D007473:Ion Channels; D005576:Colforsin; D000242:Cyclic AMP; D011188:Potassium