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Human Chorionic Gonadotrophin Relaxation of Human Pregnant Myometrium and Activation of the BK_Ca Channel

Department of Obstetrics and Gynaecology (H.C.D., D.D.H., N.R., J.J.M.), National University of Ireland Galway, Clinical Science Institute, University College Hospital Galway, Galway, Ireland; and National Centre for Biomedical Engineering Science (T.J.S.), National University of Ireland, Galway, Ireland

Address all correspondence and requests for reprints to: Professor John J. Morrison, Department of Obstetrics and Gynaecology, National University of Ireland Galway, Clinical Science Institute, University College Hospital Galway, Galway, Ireland. E-mail: john.morrison{at}nuigalway.ie.

The uterorelaxant effect of human chorionic gonadotropin (hCG) is regarded as an important mediator in maintenance of uterine quiescence during pregnancy with clinical potential for tocolysis, the mechanisms of which are unknown. The large conductance calcium-activated K⁺ channel (BK_Ca) is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate the involvement of BK_Ca channel function in the response of human myometrial cells to hCG. Single electrophysiological BK_Ca channel recordings from freshly dispersed myocytes were obtained in the presence and absence of increasing hCG concentrations. Isometric tension studies, investigating the effects of hCG on isolated myometrial contractions, in the presence and absence of the BK_Ca channel blocker, iberiotoxin, were performed. The hCG significantly increased the open-state probability of these channels in a concentration-dependent manner [control 0.036 ± 0.01; 1 IU/ml hCG 0.065 ± 0.014 (P = 0.262); 10 IU/ml hCG 0.111 ± 0.009 (P = 0.001); and 100 IU/ml hCG 0.098 ± 0.004 (P = 0.007)]. In vitro functional studies demonstrated that hCG exerted a significant concentration-dependent relaxant effect on human myometrial tissue. This effect was significantly attenuated by preincubation with iberiotoxin (P < 0.05). These findings outline that activation of BK_Ca channel activity may explain the potent uterorelaxant effect of hCG.

This work was supported by Higher Educational Authority of Ireland (PRTLI Cycle 1).

Abbreviations: BK_Ca, Calcium-activated K⁺ channel; hCG, human chorionic gonadotropin; IbTX, iberiotoxin; NP_o, mean open probability; PSS, physiologic saline solution; TEA, tetraethylammonium.

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