The effects of MCC-134 on the ATP-sensitive K+ channels in pig urethra.

We have investigated the effects of MCC-134 (1-[4-(1H-imidazol-1-yl)benzoyl]-N-methyl-cyclobutanecarbothioamide) on membrane currents and ATP-sensitive K(+) channel (K(ATP) channel) opener-induced currents in pig urethra by use of patch-clamp techniques (conventional whole-cell configuration and nystatin perforated patch recordings). Tension measurement was also performed to study the effects of MCC-134 on the resting tone of pig urethral strips. MCC-134 reduced the resting tone of pig urethra in a concentration-dependent manner (EC(50)=6 microM). The MCC-134 (30 microM)-induced relaxation was suppressed by glibenclamide. In voltage-clamp experiments, MCC-134 produced a concentration-dependent inward K(+) current which was suppressed by application of glibenclamide at a holding potential of -50 mV (symmetrical 140 mM K(+) conditions). Application of MCC-134 enhanced diazoxide-induced inward currents and inhibited pinacidil-induced inward currents in a concentration-dependent manner at -50 mV. These results suggest that MCC-134 induces glibenclamide-sensitive K(ATP) currents in pig urethra.