KATP channels are up-regulated with increasing age in human myometrium

It is well established that ageing is associated with decrease in myometrial efficiency and higher incidence of labour complications. In myometrium, the presence of ATP-sensitive K+ (KATP) channels has been detected and they could be a factor in regulating uterine quiescence in pregnancy and contractions during labour. Here, we have examined a possibility of ageing-mediated regulation of KATP channels in the human myometrium. Myometrial samples were taken from non-pregnant women undergoing hysterectomy (n = 34) and from women undergoing caesarean section in late pregnancy (n = 36). Real time RT-PCR revealed that mRNAs of all known KATP channel subunits were present in the human myometrium. In non-pregnant myometrium, ageing up-regulated SUR2B/Kir6.1, subunits forming KATP channels in this tissue, without affecting the expression of other channel subunits. In the late pregnant myometrium, the level of subunits that do not form functional KATP channels was not affected by age within 20–41 age range. However, uterine SUR2B and Kir6.1 were up-regulated in parturient over 35 years. An ageing-induced increase in those channel subunits was confirmed by Western blotting. Thus, this study suggests that KATP channels are up-regulated with increasing age in human myometrium. This may help explain, at least partially, increased rate of birth complications in women aged over 35 years.

► Ageing up-regulates KATP channels in non-pregnant human uterus.
► Late pregnancy is associated with down-regulation of KATP channels in human uterus.
► Specifically after age of 35, ageing up-regulates KATP channels in late-pregnant human uterus.
► These findings can explain increase in birth rate complications in partiurent over 35.