Effects of K+ channel inhibitors and antagonists on NS-004 evoked relaxations in guinea-pig isolated trachea.

ABSTRACT

The smooth muscle relaxant responses to NS-004, an activator of charybdotoxin-sensitive, large conductance Ca(2+)-dependent K+ channels (BKCa) were studied on the basal spontaneous tone in guinea-pig trachea in vitro. The sensitivity of these responses to a range of K+ channel inhibitors and antagonists were also evaluated. NS-004 (0.1-30 microM) evoked concentration-related relaxations (pIC50 5.48 +/- 0.13) on the spontaneous tone in guinea-pig tracheal rings, suspended in Krebs bicarbonate solution, with a maximum response not different to that to aminophylline (1 microM). Charybdotoxin (0.03 and 0.1 microM) or iberiotoxin (0.1 microM) significantly displaced the NS-004 concentration-response curve to the right of control with no change in maximum response. In contrast, glibenclamide (1.0 microM) apamin (0.1 microM) and dofetilide (1.0 microM) each failed to modify the responses to NS-004 on spontaneous tone in guinea-pig trachea. These results suggest that relaxations in guinea-pig tracheal smooth muscle to the substituted benzimidazolone, NS-004, involve the activation of BKCa channels.