Differential effects of the BKCa channel openers NS004 and NS1608 in porcine coronary arterial cells.

The effects of newly claimed BKCa channel openers NS004 (5-trifluoromethyl-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-2H-benzimidazo le-2- one) and NS1608 (N-(3-(trifluoromethyl)phenyl)-N'-(2-hydroxy-5-chlorophenyl)urea) were investigated on whole-cell K+ current (IK) in enzymatically isolated porcine coronary arterial cells using patch-clamp technique with a double holding potential protocol. When cells were held at 0 mV, IK was augmented by NS004 in a concentration-dependent manner. With a holding potential of -60 mV, however, IK was moderately inhibited by NS004 between 0.5 and 10 microM, but robustly stimulated by 50 microM NS004 at highly depolarized potentials. The effects of NS1608 on IK did not differ due to change in holding potential. At -60 mV and 0 mV, NS1608 activated IK with bell-shaped concentration-response curves peaked between 5 and 10 microM. The differential mode of action of the two compounds suggested an involvement of mechanism(s) other than an opening of BKCa channel.