title: The stretch-dependent potassium channel TREK-1 and its function in murine myometrium.
abstract: Smooth muscle of the uterus stays remarkably quiescent during normal pregnancy to allow sufficient time for development of the fetus. At present the mechanisms leading to uterine quiescence during pregnancy and how the suppression of activity is relieved at term are poorly understood. Myometrial excitability is governed by ion channels, and a major hypothesis regarding the regulation of contractility during pregnancy has been that expression of certain channels is regulated by hormonal influences. We have explored the expression and function of stretch-dependent K+ (SDK) channels, which are likely to be due to TREK channels, in murine myometrial tissues and myocytes using PCR, Western blots, patch clamp, intracellular microelectrode and isometric force measurements. TREK-1 is more highly expressed than TREK-2 in myometrium, and there was no detectable expression of TRAAK. Expression of TREK-1 transcripts and protein was regulated during pregnancy and delivery. SDK channels were activated in response to negative pressure applied to patches. SDK channels were insensitive to a broad-spectrum of K+ channel blockers, including tetraethylammonium and 4-aminopyridine, and insensitive to intracellular Ca2+. SDK channels were activated by stretch and arachidonic acid and inhibited by reagents that block TREK-1 channels, l-methionine and/or methioninol. Our data suggest that uterine excitability and contractility during pregnancy is regulated by the expression of SDK/TREK-1 channels. Up-regulation of these channels stabilizes membrane potential and controls contraction during pregnancy and down-regulation of these channels induces the onset of delivery.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Monaghan
authors.forename: Salah A
authors.initials: SA
authors.lastname: Baker
authors.forename: Laura
authors.initials: L
authors.lastname: Dwyer
authors.forename: William C
authors.initials: WC
authors.lastname: Hatton
authors.forename: Kyung
authors.initials: K
authors.lastname: Sik Park
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Sang Don
authors.initials: SD
authors.lastname: Koh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008839:Microelectrodes; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism*; D010052:Ovariectomy; D036801:Parturition / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology
chemical_list: D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C103742:potassium channel protein TREK-1