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()
S. Macmillan et al., 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(), British Journal of Pharmacology, 116(1), 1995, pp. 1656-1660
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 BKC
a 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 c
hannel 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 concent
ration-related increases in open state probability of BKCa channels wh
en applied to either inside-out or outside-out BTSM patches, thus conf
irming 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 B
KCa 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 c
hannel activity in BTSM patches and that the previously reported relax
ant action of SCA40 on tracheal smooth muscle is unlikely to be mediat
ed by this mechanism.