A COMPARISON OF THE EFFECTS OF SCA40, NS-004 AND NS-1619 ON LARGE-CONDUCTANCE CA2+-ACTIVATED K+ CHANNELS IN BOVINE TRACHEAL SMOOTH-MUSCLE CELLS IN CULTURE

1 The effects of imidazopyrazine derivative, SCA40, on the activity of single large conductance, Ca2+-activated K+ (BKCa) channels in inside-out and outside-out patches from bovine tracheal smooth muscle (BTSM) cells in culture have been compared with those of two established BKCa channel openers, NS 004 and NS 1619. 2 The presence of BKCa channels on inside-out patches of BTSM membranes was confirmed by the single channel conductance (240 pS), selectivity for K+, dependence of channel activity on [Ca2+](i), and sensitivity to the selective BKCa channel blocker, iberiotoxin. 3 NS 004 and ND 1619 (3-30 mu M) induced concentration-related increases in open state probability of BKCa channels when applied to either inside-out or outside-out BTSM patches, thus confirming that these compounds are activators of the BKCa channel in this preparation. 4 SCA40 (0.1-10 mu M) had no effect on the activity of BKCa channels when applied to either inside-out or outside-out patches which subsequently responded to the application of NS 004 (10-20 mu M). 5 It is concluded that SCA40 does not have a direct effect on BKCa channel activity in BTSM patches and that the previously reported relaxant action of SCA40 on tracheal smooth muscle is unlikely to be mediated by this mechanism.