Activation of KV7 channels stimulates vasodilatation of human placental chorionic plate arteries

Introduction: Potassium (K+) channels are key regulators of vascular smooth muscle cell (VSMC) excitability. In systemic small arteries, K(V)7 channel expression/activity has been noted and a role in vascular tone regulation demonstrated. We aimed to demonstrate functional K(V)7 channels in human fetoplacental small arteries. Methods: Human placental chorionic plate arteries (CPAs) were obtained at term. CPA responses to K(V)7 channel modulators was determined by wire myography. Presence of K(V)7 channel mRNA (encoded by KCNQ1-5) and protein expression were assessed by RT-PCR and immunohistochemistry/immunofluorescence, respectively. Results: K(V)7 channel blockade with linopirdine increased CPA basal tone and AVP-induced contraction. Pre-contracted CPAs (AVP; 80 mM K+ depolarization solution) exhibited significant relaxation to flupirtine, retigabine, the acrylamide (S)-1, and (S) BMS-204352, differential activators of K(V)7.1 - K(V)7.5 channels. All CPAs assessed expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs. K(V)7 protein expression was confirmed in intact CPAs and isolated VSMCs. Discussion: K(V)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. (C) 2015 Elsevier Ltd. All rights reserved.