The relaxant effect of nifedipine in human uterine smooth muscle and the BK Ca channel

Abstract

The purpose of this study was to investigate the effects of K+ channel blockade on the uterorelaxant effects of nifedipine in human myometrium during pregnancy. Biopsies of human myometrium were obtained at elective cesarean section (n = 24). Dissected myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were subjected to K+ channel blockade using tetraethylammonium (TEA) or iberiotoxin (IbTX) followed by cumulative additions of nifedipine (1 nmol/L-10 micromol/L). Control experiments were run simultaneously. Integrals of contractile activity were measured using the PowerLab hardware unit and Chart v3.6 software. Data were analyzed using one-way analysis of variance (ANOVA) followed by post hoc analysis. Nifedipine exerted a potent and cumulative inhibitory effect on spontaneous contractions and oxytocin-induced contractions in human myometrium in vitro, in comparison to control measurements (P < .05, n = 6). Incubation of strips with TEA or IbTX, prior to addition of nifedipine, significantly attenuated the relaxant effect exerted by nifedipine (P < .05, n = 6). This study demonstrates that the uterorelaxant effect of nifedipine is attenuated by potassium channel (K+) blockade. This suggests that K+ channel conductance, and particularly the BK(Ca) channel, plays a role in the potent relaxant effect of nifedipine, hitherto presumed to act solely through L-gated calcium channels.