Variants of Stretch-Activated Two-Pore Potassium Channel TREK-1 Associated with Preterm Labor in Humans

被引:21
作者
Wu, Yi-Ying [1 ]
Singer, Cherie A. [1 ]
Buxton, Iain L. O. [1 ]
机构
[1] Univ Nevada, Sch Med, Dept Pharmacol, Reno, NV 89557 USA
基金
美国国家卫生研究院;
关键词
human; labor; myometrial smooth muscle; pregnancy; potassium channels; preterm labor; splice variants; TREK-1; uterus; K+ CHANNEL; EXPRESSION; BIRTH;
D O I
10.1095/biolreprod.112.099499
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Spontaneous preterm labor (PTL) is a uniquely human problem that results in preterm delivery of an underdeveloped fetus. The underlying cause remains elusive. The cost to societies in human suffering and treasure is enormous. The stretch-activated two pore potassium channel TREK-1 is up-regulated during gestation to term such that it may maintain uterine quiescence by hyperpolarizing the smooth muscle cell membrane. We have hypothesized that the human TREK-1 channel is involved in myometrial relaxation during pregnancy and that splice variants of the TREK-1 channel expressed in preterm myometrium are associated with preterm delivery by interaction with full-length TREK-1. We detected three wild-type human TREK-1 transcript isoforms in nonpregnant and pregnant human myometrium. Using RT-PCR, we identified five unique TREK-1 splice variants in myometrium from women in PTL. These myometrial TREK-1 variants lack either the pore or the transmembrane domains or both. In transiently transfected HEK293T cells, wild-type TREK-1 was predominantly expressed at the plasma membrane. However, individual splice variants were expressed uniformly throughout the cell. Wild-type TREK-1 was localized at the plasma membrane and cytoplasm close to the plasma membrane when coexpressed with each splice variant. Co-immunoprecipitation of FLAG epitope-tagged TREK-1 and six-His epitope-tagged splice variants using Ni bead columns successfully pulled down wild-type TREK-1. These results suggest that each of four TREK-1 splice variants interacts with full-length wild-type TREK-1 and that in vivo, such interactions may contribute to a PTL phenotype.
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页数:9
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共 21 条
[1]   Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium [J].
Bai, XL ;
Bugg, GJ ;
Greenwood, SL ;
Glazier, JD ;
Sibley, CP ;
Baker, PN ;
Taggart, MJ ;
Fyfe, GK .
REPRODUCTION, 2005, 129 (04) :525-530
[2]   The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity [J].
Beck, Stacy ;
Wojdyla, Daniel ;
Say, Lale ;
Betran, Ana Pilar ;
Merialdi, Mario ;
Requejo, Jennifer Harris ;
Rubens, Craig ;
Menon, Ramkumar ;
Van Look, Paul F. A. .
BULLETIN OF THE WORLD HEALTH ORGANIZATION, 2010, 88 (01) :31-38
[3]   Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium channel [J].
Blondeau, Nicolas ;
Petrault, Olivier ;
Manta, Stella ;
Giordanengo, Valerie ;
Gounon, Pierre ;
Bordet, Regis ;
Lazdunski, Michel ;
Heurteaux, Catherine .
CIRCULATION RESEARCH, 2007, 101 (02) :176-184
[4]   Expression of Stretch-Activated Two-Pore Potassium Channels in Human Myometrium in Pregnancy and Labor [J].
Buxton, Iain L. O. ;
Singer, Cherie A. ;
Tichenor, Jennifer N. .
PLOS ONE, 2010, 5 (08)
[5]   A phospholipid sensor controls mechanogating of the K+ channel TREK-1 [J].
Chemin, J ;
Patel, AJ ;
Duprat, F ;
Lauritzen, I ;
Lazdunski, M ;
Honoré, E .
EMBO JOURNAL, 2005, 24 (01) :44-53
[6]   Up- and down-regulation of the mechano-gated K2P channel TREK-1 by PIP2 and other membrane phospholipids [J].
Chemin, Jean ;
Patel, Amanda Jane ;
Duprat, Fabrice ;
Sachs, Frederick ;
Lazdunski, Michel ;
Honore, Eric .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2007, 455 (01) :97-103
[7]   The mechano-gated K2P channel TREK-1 [J].
Dedman, Alexandra ;
Sharif-Naeini, Reza ;
Folgering, Joost H. A. ;
Duprat, Fabrice ;
Patel, Amanda ;
Honore, Eric .
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 2009, 38 (03) :293-303
[8]   cAMP Analogs and Their Metabolites Enhance TREK-1 mRNA and K+ Current Expression in Adrenocortical Cells [J].
Enyeart, Judith A. ;
Liu, Haiyan ;
Enyeart, John J. .
MOLECULAR PHARMACOLOGY, 2010, 77 (03) :469-482
[9]   Molecular Background of Leak K+ Currents: Two-Pore Domain Potassium Channels [J].
Enyedi, Peter ;
Czirjak, Gabor .
PHYSIOLOGICAL REVIEWS, 2010, 90 (02) :559-605
[10]   Mapping a New Spontaneous Preterm Birth Susceptibility Gene, IGF1R, Using Linkage, Haplotype Sharing, and Association Analysis [J].
Haataja, Ritva ;
Karjalainen, Minna K. ;
Luukkonen, Aino ;
Teramo, Kari ;
Puttonen, Hilkka ;
Ojaniemi, Marja ;
Varilo, Teppo ;
Chaudhari, Bimal P. ;
Plunkett, Jevon ;
Murray, Jeffrey C. ;
McCarroll, Steven A. ;
Peltonen, Leena ;
Muglia, Louis J. ;
Palotie, Aarno ;
Hallman, Mikko .
PLOS GENETICS, 2011, 7 (02)