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 muM for chelerythrine and 98.69 +/- 12.68 DM 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 GTP gammaS to the bath solution in inside-out patches, chelerythrine (10 muM) 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. (C) 2001 Elsevier Science B.V. All rights reserved.