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Submitted on March 15, 2005
Accepted on July 6, 2005
3-Adrenoceptors and Large Conductance Calcium-Activated Potassium Channels in Human Uterine Myocytes
Department of Obstetrics & Gynaecology, National University of Ireland Galway, Clinical Science Institute, University College Hospital Galway, Galway, Ireland.; National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
* To whom correspondence should be addressed. E-mail: hdoheny{at}nuigalway.ie.
Context: 
3-Adrenoreceptor modulation in human myometrium during pregnancy is functionally linked to myometrial inhibition. Maxi-K+ channels (BKCa) play a significant role in modulating cell membrane potential and excitability.
Objective: To investigate the potential involvement of BKCa channel function in the response of human myometrium to 3-adrenoceptor activation.
Design: Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes were obtained in the presence and absence of BRL37344, a specific 3-adrenoreceptor agonist. The in vitro effects of BRL37344 on isolated myometrial contractions, in the presence and absence of the specific BKCa channel blocker, iberiotoxin (IbTX), were investigated.
Setting: Clinical Science Institute.
Patients or Other Participants: Myometrial biopsies were obtained at elective caesarean delivery.
Intervention: None applied.
Main Outcome Measures: Open state probability of single channel recordings, whole cell currents and myometrial contractile activity.
Results: Single-channel recordings identified the BKCa channel as a target of BRL37344. BRL37344 significantly increased the open state probability of this channel in a concentration-dependent manner (control 0.031 ± 0.004; 50 µM BRL37344 0.073 ± 0.005 (P < 0.001); and 100 µM BRL37344 0.101 ± 0.005 (P < 0.001). This effect was completely blocked following pre-incubation of the cells with 1 µM bupranolol, a non-specific -adrenoreceptor blocker or 100 nM SR59230a, a specific 3-adrenoreceptor antagonist. In addition, BRL37344 increased whole-cell currents over a range of membrane potentials and this effect was reversed by 100 nM IbTX. In vitro isometric tension studies demonstrated that BRL37344 exerted a significant concentration-dependent relaxant effect on human myometrial tissue (P < 0.05) and pre-incubation of these strips with IbTX attenuated this effect on both spontaneous and oxytocin-induced contractions (44.44% and 57.84% at 10-5M, respectively).
Conclusions: These findings outline that activation of the BKCa channel may explain, the potent uterorelaxant effect of 3-adrenoreceptor agonists.
3-Adrenoceptor •
BKCa-Channels •
Labor •
Tocolysis
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