Gestational changes in the uterine expression of an inwardly rectifying K+ channel, ROMK

We have examined the repertoire and relative expression levels of voltage-gated K+ channels in timed-pregnant rat uteri. These studies have revealed the gestation-specific and abundant expression of mRNA encoding an inwardly rectifying K+ channel, ROMK (originally identified in renal outer medulla), within the gravid uterus. Steady-state levels of ROMK transcripts undergo dynamic gestational changes: they are undetectable in virgin uteri, reach a maximum level by Day 12 of gestation, decline thereafter until, by term, they are again undetectable. Kidney cells also express ROMK transcripts at high levels but do not undergo apparent changes during gestation. Molecular analyses (by "rapid amplification of cDNA ends", or "5'-RACE") of the ROMK mRNAs revealed the presence of two alternative-splicing variants which are likely to arise from distinct transcription-start sites within the same gene. Polymerase chain reaction-based assessments of gravid uteri from other species revealed the expression of ROMK transcripts in the myometrium as well. Uterine expression of ROMK therefore represents a generalized phenomenon, characterized by both gestation- and tissue-specific regulation, and the transcription-regulatory mechanisms of this channel protein are potentially complex. From the biophysical properties of this channel in vitro and the observed gestational profile, we hypothesize that this channel modulates both the resting membrane potential and cellular excitability of myometrial cells, and in turn contributes to the observed contractile quiescence of the gravid uterus.