The expression and function of KCNQ potassium channels in human chorionic plate arteries from women with normal pregnancies and pre-eclampsia.

Abstract

Pre-eclampsia is associated with altered maternal and placental vascular reactivity. Kv7 channels (encoded by KCNQ 1-5 genes) are a potential contributor to the regulation of vascular tone in CPAs (chorionic plate arteries) during normal pregnancy. The aim of this study is to establish the expression profile of KCNQ subunits in CPAs taken from women with preeclampsia or normotensive women and to examine the functional relevance of the Kv7 channels on an altered expression profile of KCNQ subunits. The effects of Kv7 channel modulators on CPAs were investigated by tension measurement. Quantitative PCR experiments were used to analyze the expression of KCNQ genes. Western blotting and immunofluorescence were both used to analyze the protein expression of Kv7 channels. Finally, in CPAs from normotensive women, the Kv7 channel blocker XE991 increased arterial basal tone and U46619-induced contraction, and pre-contracted CPAs (10-7 M U46619) exhibited significant relaxation following treatment with Retigabine(Kv7.2-7.5 activator) and BMS-204352(Kv7.2-7.5 activator). However, ICA-27243(selective KCNQ2 and KCNQ3 activator) and ML277(selective KV7.1 activator) had no significant effect on tension in the pre-contracted CPAs. Conversely, compared with CPAs from normotensive women, the effects of XE991 on basal tone and agonist (U46619)-induced contractions in CPAs from women with preeclampsia were markedly attenuated. Moreover, the relaxation effects of Retigabine and BMS-204352 on pre-contracted CPA vessels from women with pre-eclampsia were also markedly down-regulated. Interestingly, the relaxation ability of ICA-27243 in pre-contracted CPA vessels in women with pre-eclampsia was enhanced. The mRNA of KCNQ3 was specifically up-regulated, whereas those for KCNQ4 and KCNQ5 were down-regulated in CPAs from women with pre-eclampsia compared with those in normotensive women. Similar observations were found in a subsequent analysis of protein expression of KCNQ genes 3-5. Thus, down-regulated Kv7 channel function in tension regulation of CPAs in women with pre-eclampsia could be associated with considerably altered expression profiles of Kv7 subunits.