KV7 channel activation inhibits human and murine myometrium contractility and delays delivery in a mouse model of preterm birth

Despite spontaneous preterm birth (PTB, delivery < 37 weeks’ gestation) being a major contributor to perinatal morbidity and mortality worldwide, there is a paucity of treatments for treating preterm labor. We hypothesized that uterine smooth muscle (myometrium) Kv7 channels could be a therapeutic target for preventing preterm labor. Building on our previous work, we confirmed that K _V 7 channels, proteins encoded by KCNQ2-5 genes and associated accessory KCNE1-5, are expressed and functional in pregnant human myometrium prior to and after the onset of labor. K _V 7.2-5 activators (retigabine and ML213) effectively inhibit pregnant human and mouse myometrium contractions in vitro , and in vivo significantly delayed PTB in a non-infection preterm labor mouse model. This supports our hypothesis that augmenting K _V 7 activity represents a viable mechanism to suppress uterine contractility and delay of PTB. Addressing the current drive to repurpose existing drugs for treating PTB, we propose this as a new avenue of clinical exploration. One Sentence Summary : K _V 7 channel activators inhibit human uterine contractions and delay delivery in preterm mice, identifying a new target for preterm labor prevention.