Activation of K<inf>V</inf>7 channels stimulates vasodilatation of human placental chorionic plate arteries
Mills TA., Greenwood SL., Devlin G., Shweikh Y., Robinson M., Cowley E., Hayward CE., Cottrell EC., Tropea T., Brereton MF., Dalby-Brown W., Wareing M.
© 2015 Elsevier Ltd.Introduction Potassium (K<sup>+</sup>) channels are key regulators of vascular smooth muscle cell (VSMC) excitability. In systemic small arteries, K<inf>v</inf>7 channel expression/activity has been noted and a role in vascular tone regulation demonstrated. We aimed to demonstrate functional K<inf>v</inf>7 channels in human fetoplacental small arteries. Methods Human placental chorionic plate arteries (CPAs) were obtained at term. CPA responses to K<inf>v</inf>7 channel modulators was determined by wire myography. Presence of K<inf>v</inf>7 channel mRNA (encoded by KCNQ1-5) and protein expression were assessed by RT-PCR and immunohistochemistry/immunofluorescence, respectively. Results K<inf>v</inf>7 channel blockade with linopirdine increased CPA basal tone and AVP-induced contraction. Pre-contracted CPAs (AVP; 80 mM K<sup>+</sup> depolarization solution) exhibited significant relaxation to flupirtine, retigabine, the acrylamide (S)-1, and (S) BMS-204352, differential activators of K<inf>v</inf>7.1 - K<inf>v</inf>7.5 channels. All CPAs assessed expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs. K<inf>v</inf>7 protein expression was confirmed in intact CPAs and isolated VSMCs. Discussion K<inf>v</inf>7 channels are present and active in fetoplacental vessels, contributing to vascular tone regulation in normal pregnancy. Targeting these channels may represent a therapeutic intervention in pregnancies complicated by increased vascular resistance.