title: Expression of stretch-activated two-pore potassium channels in human myometrium in pregnancy and labor.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Nevada, Reno, Nevada, United States of America. ibuxton@medicine.nevada.edu
authors.forename: Iain L O
authors.initials: IL
authors.lastname: Buxton
authors.forename: Cherie A
authors.initials: CA
authors.lastname: Singer
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Tichenor
mesh_terms: D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007743:Labor, Obstetric / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
chemical_list: C503432:KCNK4 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1
references.citation: Trends Neurosci. 2001 Jun;24(6):339-46
references.pmid: 11356506
references.citation: Reproduction. 2005 Apr;129(4):525-30
references.pmid: 15798028
references.citation: Nature. 2004 Jul 8;430(6996):235-40
references.pmid: 15241420
references.citation: J Physiol. 2006 Jan 1;570(Pt 1):37-43
references.pmid: 16239268
references.citation: AACN Clin Issues. 2000 May;11(2):271-82
references.pmid: 11235436
references.citation: J Biol Chem. 2001 Nov 23;276(47):44338-46
references.pmid: 11560940
references.citation: Toxicon. 2007 Feb;49(2):249-70
references.pmid: 17157345
references.citation: Semin Cell Dev Biol. 2007 Jun;18(3):332-9
references.pmid: 17596977
references.citation: Clin Exp Pharmacol Physiol. 2004 Mar;31(3):174-8
references.pmid: 15008961
references.citation: Drug Saf. 1999 Jul;21(1):35-56
references.pmid: 10433352
references.citation: Pflugers Arch. 2000 Apr;439(6):714-22
references.pmid: 10784345
references.citation: Proc West Pharmacol Soc. 2002;45:184-6
references.pmid: 12434576
references.citation: Am J Physiol Heart Circ Physiol. 2008 May;294(5):H2012-21
references.pmid: 18344374
references.citation: Brain Res Mol Brain Res. 2001 Jan 31;86(1-2):101-14
references.pmid: 11165377
references.citation: Cardiovasc Res. 2006 Jan;69(1):86-97
references.pmid: 16248991
references.citation: J Clin Endocrinol Metab. 2006 Feb;91(2):597-606
references.pmid: 16291703
references.citation: South Med J. 2009 Sep;102(9):900-4
references.pmid: 19668021
references.citation: Exp Physiol. 2004 May;89(3):237-42
references.pmid: 15123558
references.citation: Biochem Soc Trans. 2007 Nov;35(Pt 5):1069-73
references.pmid: 17956281
references.citation: Br J Pharmacol. 2005 Apr;144(8):1126-37
references.pmid: 15700022
references.citation: Am J Physiol Cell Physiol. 2005 Jul;289(1):C49-57
references.pmid: 15703204
references.citation: NCHS Data Brief. 2008 Oct;(9):1-8
references.pmid: 19389323
references.citation: J Physiol. 1999 Dec 1;521 Pt 2:337-50
references.pmid: 10581306
references.citation: Br J Pharmacol. 1996 Oct;119(4):737-43
references.pmid: 8904649
references.citation: Proc West Pharmacol Soc. 2003;46:74-7
references.pmid: 14699891
references.citation: J Huazhong Univ Sci Technolog Med Sci. 2006;26(1):31-3
references.pmid: 16711001
references.citation: J Gen Physiol. 2000 May;115(5):583-98
references.pmid: 10779316
references.citation: Proc West Pharmacol Soc. 2005;48:44-8
references.pmid: 16416658
references.citation: Am J Physiol Cell Physiol. 2003 Sep;285(3):C529-38
references.pmid: 12724142
references.citation: Neuron. 2003 May 8;38(3):417-32
references.pmid: 12741989
references.citation: J Neurosci. 2001 Oct 1;21(19):7491-505
references.pmid: 11567039
references.citation: Placenta. 2003 Apr;24 Suppl A:S33-46
references.pmid: 12842412
references.citation: Br J Pharmacol. 2001 Sep;134(1):206-14
references.pmid: 11522613
references.citation: J Biol Chem. 2000 Sep 8;275(36):27712-9
references.pmid: 10871603
references.citation: Anesthesiology. 2001 Oct;95(4):1013-21
references.pmid: 11605899
references.citation: Am J Obstet Gynecol. 2005 May;192(5 Suppl):S47-55
references.pmid: 15891712
references.citation: Mol Hum Reprod. 2002 Oct;8(10):941-5
references.pmid: 12356945
references.citation: Reprod Biol Endocrinol. 2004 Sep 21;2:67
references.pmid: 15383146
references.citation: Br J Pharmacol. 2008 Mar;153(6):1259-71
references.pmid: 18204472
references.citation: Obstet Gynecol. 2008 Jul;112(1):127-34
references.pmid: 18591318
references.citation: Eur J Obstet Gynecol Reprod Biol. 2009 Jan;142(1):3-11
references.pmid: 18996637
references.citation: Bull World Health Organ. 2010 Jan;88(1):31-8
references.pmid: 20428351
references.citation: Trends Pharmacol Sci. 2003 Dec;24(12):648-54
references.pmid: 14654306
references.citation: J Physiol. 2002 Mar 15;539(Pt 3):657-68
references.pmid: 11897838
references.citation: J Reprod Med. 2009 Feb;54(2):47-52
references.pmid: 19301566
references.citation: Int J Gynaecol Obstet. 2003 Jul;82(1):127-35
references.pmid: 12834934
references.citation: Biochem Biophys Res Commun. 2005 Feb 25;327(4):1163-9
references.pmid: 15652517
references.citation: EMBO J. 1998 Jun 15;17(12):3297-308
references.pmid: 9628867
references.citation: Lancet. 2008 Jan 5;371(9606):75-84
references.pmid: 18177778
references.citation: Biochem Biophys Res Commun. 2007 Mar 2;354(1):284-9
references.pmid: 17222806
references.citation: J Physiol. 2008 Feb 15;586(4):1169-84
references.pmid: 18187470