Premium
Trek‐1 Splice Variants May Lead To Failure of Human Myometrial Relaxation And Contribute To Preterm Labor
Author(s) -
Wu YiYing,
Singer Cherie,
Buxton Iain L. O.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1115.21
Subject(s) - myometrium , pregnancy , microbiology and biotechnology , biology , medicine , endocrinology , andrology , genetics
Spontaneous preterm labor (PTL) is a uniquely human problem that results in preterm delivery of an underdeveloped fetus, and the cause(s) is unknown. TREK‐1, a member of the two pore domain, plays an essential role in setting the resting membrane potential. We have shown that TREK‐1 is up‐regulated during pregnancy toward term for maintaining uterine quiescence by hyperpolarizing the cell membrane. Our hypothesis is that TREK‐1 plays an essential role in human myometrial relaxation during pregnancy and splice variants of the TREK‐1 channel are associated with PTL. Using RT‐PCR, we have identified five unique TREK‐1 slicing variants in preterm pregnancy tissue. The unique myometrial TREK‐1variants lack either pore or transmembrane domains or both. We have pulled down a unique myometrial TREK‐1 variant form preterm myometrium. Cloning and stable expression of TREK‐1 variants in human cells either lacking or containing native TREK‐1 is underway to characterize variant channel function electrophysiologically, while real‐time PCR studies will permit correlation of variant expression with the clinical presentation of spontaneous preterm labor. Supported by March of Dimes Prematurity Initiative Grant 21‐FY10‐176 and NIH HD053028 to ILOB.