GESTATIONAL CHANGES IN THE UTERINE EXPRESSION OF AN INWARDLY RECTIFYING K+ CHANNEL, ROMK

We have examined the repertoire and relative expression levels of volt age-gated K+ channels in timed-pregnant rat uteri, These studies have revealed the gestation-specific and abundant expression of mRNA encodi ng an inwardly rectifying K+ channel, ROMK (originally identified in r enal outer medulla), within the gravid uterus, Steady-state levels of ROMK transcripts undergo dynamic gestational changes: they are undetec table in virgin uteri, reach a maximum level by Day 12 of gestation, d ecline 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 ampl ification of cDNA ends, or ''5'-RACE'') of the ROMK mRNAs revealed the presence of two alternative-splicing variants which are likely to ari se from distinct transcription-start sites within the same gene. Polym erase chain reaction-based assessments of gravid uteri from other spec ies revealed the expression of ROMK transcripts in the myometrium as w ell. Uterine expression of ROMK therefore represents a generalized phe nomenon, characterized by both gestation- and tissue-specific regulati on, and the transcription-regulatory mechanisms of this channel protei n are potentially complex. From the biophysical properties of this cha nnel in vitro and the observed gestational profile, we hypothesize tha t this channel modulates both the resting membrane potential and cellu lar excitability of myometrial cells, and in turn contributes to the o bserved contractile quiescence of the gravid uterus.