Audrey T Moynihan1, Terry J Smith, John J Morrison. 1. Department of Obstetrics and Gynaecology, Clinical Science Institute, University College Hospital Galway, Galway, Ireland, UK.
Abstract
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. STUDY DESIGN: 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). CONCLUSION: 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.
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. STUDY DESIGN: 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). CONCLUSION: 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.
Authors: Kaizhi Zheng; Ping Lu; Ellen Delpapa; Karl Bellve; Ruitang Deng; Jennifer C Condon; Kevin Fogarty; Lawrence M Lifshitz; Tiffany A Moore Simas; Fangxiong Shi; Ronghua ZhuGe Journal: FASEB J Date: 2017-05-30 Impact factor: 5.191
Authors: Monali Wakle-Prabagaran; Ramón A Lorca; Xiaofeng Ma; Susan J Stamnes; Chinwendu Amazu; Jordy J Hsiao; Celeste M Karch; Krzysztof L Hyrc; Michael E Wright; Sarah K England Journal: Proc Natl Acad Sci U S A Date: 2016-04-04 Impact factor: 11.205