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dc.contributor.authorDoheny, Helen C.
dc.contributor.authorLynch, Caoimhe M.
dc.contributor.authorSmith, Terry
dc.contributor.authorMorrison, John J.
dc.identifier.citationDoheny, HC,Lynch, CM,Smith, TJ,Morrison, JJ (2005) 'Functional coupling of beta(3)-adrenoceptors and large conductance calcium-activated potassium channels in human uterine myocytes'. Journal Of Clinical Endocrinology & Metabolism, 90 :5786-5796.en_US
dc.descriptionJournal articleen_US
dc.description.abstractContext: beta(3)-Adrenoreceptor modulation in human myometrium during pregnancy is linked functionally to myometrial inhibition. Maxi-K+ channels (BKCa) play a significant role in modulating cell membrane potential and excitability.Objective: This study was designed to investigate the potential involvement of BKCa channel function in the response of human myometrium to beta(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 beta(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: The study was carried out at the Clinical Science Institute. Patients orOther Participants: Myometrial biopsies were obtained at elective cesarean delivery.Intervention: No intervention was applied.Main Outcome Measures: Open state probability of single channel recordings, whole cell currents, and myometrial contractile activity were measured.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 mu M BRL37344 0.073 +/- 0.005 (P < 0.001); and 100 mu M BRL37344 0.101 +/- 0.005 ( P < 0.001). This effect was completely blocked after preincubation of the cells with 1 mu M bupranolol, a nonspecific - adrenoreceptor blocker, or 100 nM SR59230a, a specific beta(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 concentrationdependent relaxant effect on human myometrial tissue (P < 0.05), and preincubation of these strips with IbTX attenuated this effect on both spontaneous and oxytocin- induced contractions (44.44 and 57.84% at 10(-5) M, respectively).Conclusions: These findings outline that activation of the BKCa channel may explain the potent uterorelaxant effect of beta(3)-adrenoreceptor agonists.en_US
dc.description.sponsorshipHealth Research Board (HRB) Ireland; HEA Ireland (Programme for Research in Third Level Institutions Cycle 1)en_US
dc.publisherEndocrine Societyen_US
dc.relation.ispartofJournal Of Clinical Endocrinology & Metabolismen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.subjectDependent protein-kinaseen_US
dc.subjectHuman pregnant myometriumen_US
dc.subjectBKCA channelen_US
dc.subjectPreterm laboren_US
dc.subjectK+ channelsen_US
dc.subjectIn vitroen_US
dc.titleFunctional coupling of beta(3)-adrenoceptors and large conductance calcium-activated potassium channels in human uterine myocytesen_US
dc.identifier.doiDOI 10.1210/jc.2005-0574
dc.local.contactTerry Smith, School Of Natural Sciences, Nui Galway. 2022 Email:

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