Abstract

The effects of nicorandil on ionic currents recorded from single smooth muscle cells of pig proximal urethra were investigated using patch-clamp techniques. Tension measurement was also performed to study the effects of nicorandil on the resting tone of pig urethra. Nicorandil produced a concentration-dependent sustained outward current that was suppressed by glibenclamide at −50 mV and was carried selectively by K⁺. In cell-attached configuration, nicorandil activated a 43-pS K⁺ channel that was reversibly inhibited by 10 μM glibenclamide. This glibenclamide-sensitive 43-pS K⁺ channel (K_GS) “ran down” after excision of the membrane patch. In inside-out configuration, the application of either 1 mM Mg-ATP or 1 mM nucleotide diphosphate reactivated the K_GS. In symmetrical 140 mM K⁺ conditions, 300 μM nicorandil and 300 μM levcromakalim activated a 2.14-pA K⁺ channel that exhibited the same amplitude and similar channel-opening kinetics. Methylene blue (10–100 μM), a soluble guanylate cyclase inhibitor, did not inhibit the opening of the nicorandil-induced K_GS. The K_GS was not activated by either sodium nitroprusside (10–100 μM) or 8-bromo guanosine 3′:5′-cyclic monophosphate (1 mM). Nicorandil caused a concentration-dependent relaxation of the urethral resting tone but was less potent than levcromakalim. The relaxation induced by 10 μM nicorandil was partially inhibited by glibenclamide (1–10 μM) and also by methylene blue (10–100 μM). These results indicate that two independent nicorandil-induced relaxation mechanisms may be present in pig urethra.