Trek‐1 Splice Variants May Lead To Failure of Human Myometrial Relaxation And Contribute To Preterm Labor

Abstract

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.