Inhibition of acetylcholine-activated K(+) current by chelerythrine and bisindolylmaleimide I in atrial myocytes from mice.
The effects of the protein kinase C inhibitors chelerythrine and bisindolylmaleimide I on acetylcholine-activated K+ currents (I(KACh)) were examined in atrial myocytes of mice, using the patch clamp technique. Chelerythrine and bisindolylmaleimide I inhibited I(KACh) in a reversible and dose-dependent manner. Half-maximal effective concentrations were 0.49+/-0.01 microM for chelerythrine and 98.69+/-12.68 nM for bisindolylmaleimide I. However, I(KACh) was not affected either by calphostin C, which is also known as a protein kinase C inhibitor, or by a protein kinase C activator, phorbol 12,13-dibutyrate. When K(ACh) channels were activated directly by adding 1 mM GTPgammaS to the bath solution in inside-out patches, chelerythrine (10 microM) decreased the open probability from 0.043+/-0.01 to 0.014+/-0.007 (n=5), but bisindolylmaleimide I did not affect the channel activity. From these results, it is concluded that both chelerythrine and bisindolylmaleimide I inhibit K(ACh) channels independently of protein kinase C inhibition, but the level of inhibition is different.
Cho
H
H
National Research Laboratory for Cellular Signalling, Seoul National University College of Medicine, 28 Yonkeun-Dong, Chongno-Ku, Seoul 110-799, South Korea.
Youm
J B
JB
Earm
Y E
YE
Ho
W K
WK
D000109:Acetylcholine / Q000494:pharmacology*; D000470:Alkaloids; D000818:Animals; D016275:Atrial Function; D053119:Benzophenanthridines; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D009281:Naphthalenes; D010617:Phenanthridines; D015221:Potassium Channels; D015240:Phorbol 12,13-Dibutyrate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C016299:chelerythrine; D011493:Protein Kinase C; C058819:calphostin C; C070515:bisindolylmaleimide I; D000109:Acetylcholine