The relaxant effect of nifedipine in human uterine smooth muscle and the BK(Ca) channel.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Moynihan
Audrey T
AT
Department of Obstetrics and Gynaecology, Clinical Science Institute, University College Hospital Galway, Galway, Ireland, UK.
Smith
Terry J
TJ
Morrison
John J
JJ
D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007752:Obstetric Labor, Premature / Q000517:prevention & control; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D002121:Calcium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D015149:Tocolytic Agents; D009543:Nifedipine