DIFFERENTIAL-EFFECTS OF THE BKCA CHANNEL OPENERS NS004 AND NS1608 IN PORCINE CORONARY ARTERIAL CELLS

The effects of newly claimed BKCa channel openers NS004 hydroxyphenyl) -1,3-dihydro-2H-benzimidazole-2-one) and NS1608 omethyl)phenyl)-N'-(2- hydroxy-5-chlorophenyl)urea) were investigated on whole-cell K+ curren t (I-K) in enzymatically isolated porcine coronary arterial cells usin g patch-clamp technique with a double holding potential protocol. When cells were held at 0 mV, I-K was augmented by NS004 in a concentratio n-dependent manner. With a holding potential of -60 mV, however, I-K w as moderately inhibited by NS004 between 0.5 and 10 mu M, but robustly stimulated by 50 mu M NS004 at highly depolarized potentials. The eff ects of NS1608 on I-K did not differ due to change in holding potentia l. At -60 mV and 0 mV, NS1608 activated I-K with bell-shaped concentra tion-response curves peaked between 5 and 10 mu M. The differential mo de of action of the two compounds suggested an involvement of mechanis m(s) other than an opening of BKCa channel.