Myometrial expression of small conductance Ca2+-activated K + channels depresses phasic uterine contraction

Amber Brown, Trudy Cornwell, Iryna Korniyenko, Viktoriya Solodushko, Chris T. Bond, John P. Adelman, Mark S. Taylor

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Mechanisms regulating uterine contractility are poorly understood. We hypothesized that a specific isoform of small conductance Ca2+- activated K+ (SK) channel, SK3, promotes feedback regulation of myometrial Ca2+ and hence relaxation of the uterus. To determine the specific functional impact of SK3 channels, we assessed isometric contractions of uterine strips from genetically altered mice (SK3T/T), in which SK3 is overexpressed and can be suppressed by oral administration of doxycycline (SK3T/T+Dox). We found SK3 protein in mouse myometrium, and this expression was substantially higher in SK3T/T mice and lower in SK3T/T+Dox mice compared with wild-type (WT) controls. Sustained contractions elicited by 60 mM KCl were not different among SK3T/T, SK3T/T+Dox, and WT mice. However, the rate of onset and magnitude of spontaneously occurring phasic contractions was muted significantly in isolated uterine strips from SK3T/T mice compared with those from WT mice. These spontaneous contractions were augmented greatly by blockade of SK channels with apamin or by suppression of SK3 expression. Phasic but not tonic contraction in response to oxytocin was depressed in uterine strips from SK3T/T mice, whereas suppression of SK3 channel expression or treatment with apamin promoted the predominance of large coordinated phasic events over tone. Spontaneous contractions and the phasic component of oxytocin contractions were blocked by nifedipine but not by cyclopiazonic acid. Our findings suggest that SK3 channels play an important role in regulating uterine function by limiting influx through L-type Ca2+ channels and disrupting the development of concerted phasic contractile events.

Original languageEnglish (US)
Pages (from-to)C832-C840
JournalAmerican Journal of Physiology - Cell Physiology
Volume292
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Ca-activated K channel
  • Doxycycline
  • Mouse
  • Uterus

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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    Brown, A., Cornwell, T., Korniyenko, I., Solodushko, V., Bond, C. T., Adelman, J. P., & Taylor, M. S. (2007). Myometrial expression of small conductance Ca2+-activated K + channels depresses phasic uterine contraction. American Journal of Physiology - Cell Physiology, 292(2), C832-C840. https://doi.org/10.1152/ajpcell.00268.2006