Expression of stretch-activated two-pore potassium channels in human myometrium in pregnancy and labor

PLoS One. 2010 Aug 25;5(8):e12372. doi: 10.1371/journal.pone.0012372.

Abstract

Background: We tested the hypothesis that the stretch-activated, four-transmembrane domain, two pore potassium channels (K2P), TREK-1 and TRAAK are gestationally-regulated in human myometrium and contribute to uterine relaxation during pregnancy until labor.

Methodology: We determined the gene and protein expression of K2P channels in non-pregnant, pregnant term and preterm laboring myometrium. We employed both molecular biological and functional studies of K2P channels in myometrial samples taken from women undergoing cesarean delivery of a fetus.

Principal findings: TREK-1, but not TREK-2, channels are expressed in human myometrium and significantly up-regulated during pregnancy. Down-regulation of TREK-1 message was seen by Q-PCR in laboring tissues consistent with a role for TREK-1 in maintaining uterine quiescence prior to labor. The TRAAK channel was unregulated in the same women. Blockade of stretch-activated channels with a channel non-specific tarantula toxin (GsMTx-4) or the more specific TREK-1 antagonist L-methionine ethyl ester altered contractile frequency in a dose-dependent manner in pregnant myometrium. Arachidonic acid treatment lowered contractile tension an effect blocked by fluphenazine. Functional studies are consistent with a role for TREK-1 in uterine quiescence.

Conclusions: We provide evidence supporting a role for TREK-1 in contributing to uterine quiescence during gestation and hypothesize that dysregulation of this mechanism may underlie certain cases of spontaneous pre-term birth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Expression Regulation* / drug effects
  • Humans
  • In Vitro Techniques
  • Labor, Obstetric / genetics*
  • Labor, Obstetric / metabolism*
  • Labor, Obstetric / physiology
  • Muscle Relaxation* / drug effects
  • Myometrium / drug effects
  • Myometrium / metabolism*
  • Myometrium / physiology
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Pregnancy
  • Premature Birth / genetics
  • Premature Birth / metabolism
  • Premature Birth / physiopathology
  • Young Adult

Substances

  • KCNK4 protein, human
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1