Calcium signaling and uterine contractility

Susan Wray, K. Jones, S. Kupittayanant, Y. Li, A. Matthew, E. Monir-Bishty, K. Noble, S. J. Pierce, S. Quenby, A. V. Shmygol

Research output: Contribution to journalReview articlepeer-review

157 Citations (Scopus)

Abstract

Changes in Ca2+ signals within the myometrium have important functional consequences, as they determine contractility. We show that the basic phasic nature of uterine contractions, which is essential for successful labor, is critically dependent on Ca2+ influx through voltage-gated L-type Ca2+ channels, and hence in turn, on membrane potential. Thus changes in ion channel expression around term will play an important role in governing uterine excitability and contractility. There remains uncertainty about which channels are present in human myometrium and the nature of the pacemaker mechanism that initiates the action potential. The sarcoplasmic reticulum may augment, to a small extent, the necessary increase in [Ca2+] for contraction when agonists stimulate the uterus, but its main role appears to be to control excitability, acting as a negative feedback mechanism to limit contractions. Myosin light chain kinase activity and phosphorylation of myosin are essential components in the pathway of uterine contraction, once Ca2+ has been elevated. Modulation of myosin light chain phosphatase activity can also influence contractions, but the effects are small compared with those modulating myosin light chain kinase. Ca2+-sensitizing pathways may not be utilized much in modulating normal phasic uterine activity, and caution is needed in extrapolating from in vitro experiments to in vivo conditions, especially because there may be redundant pathways. There is a need to study appropriate physiologic preparations, but these are not always available (eg, preterm laboring myometrium) and to combine functional studies with modern molecular approaches, to advance our understanding to a new level, from which better therapeutics will be developed.

Original languageEnglish
Pages (from-to)252-264
Number of pages13
JournalJournal of the Society for Gynecologic Investigation
Volume10
Issue number5
DOIs
Publication statusPublished - Jul 2003
Externally publishedYes

Keywords

  • Agonists
  • Contractions
  • Ion channels
  • Myometrium
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

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