T A Mills1, S L Greenwood2, G Devlin3, Y Shweikh4, M Robinson4, E Cowley5, C E Hayward6, E C Cottrell7, T Tropea8, M F Brereton9, W Dalby-Brown10, M Wareing11. 1. School of Nursing, Midwifery and Social Work, The University of Manchester, Jean McFarlane Building, Oxford Road, Manchester M13 9PL, United Kingdom. Electronic address: tracey.mills@manchester.ac.uk. 2. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. Electronic address: susan.l.greenwood@manchester.ac.uk. 3. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. Electronic address: gdevlin6@doctors.org.uk. 4. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. 5. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. Electronic address: elizabeth.cowley@manchester.ac.uk. 6. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. Electronic address: christina.hayward@manchester.ac.uk. 7. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. Electronic address: elizabeth.Cottrell@manchester.ac.uk. 8. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom; Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, CS, Italy. Electronic address: teresa_tropea@libero.it. 9. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. Electronic address: melissa.brereton@dpag.ox.ac.uk. 10. Pcovery Aps, Thorvaldsensvej 57, DK-1871 Frederiksberg C, Denmark. Electronic address: wdalbybrown@gmail.com. 11. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. Electronic address: mark.wareing@manchester.ac.uk.
Abstract
INTRODUCTION: Potassium (K(+)) channels are key regulators of vascular smooth muscle cell (VSMC) excitability. In systemic small arteries, Kv7 channel expression/activity has been noted and a role in vascular tone regulation demonstrated. We aimed to demonstrate functional Kv7 channels in human fetoplacental small arteries. METHODS: Human placental chorionic plate arteries (CPAs) were obtained at term. CPA responses to Kv7 channel modulators was determined by wire myography. Presence of Kv7 channel mRNA (encoded by KCNQ1-5) and protein expression were assessed by RT-PCR and immunohistochemistry/immunofluorescence, respectively. RESULTS: Kv7 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 Kv7.1 - Kv7.5 channels. All CPAs assessed expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs. Kv7 protein expression was confirmed in intact CPAs and isolated VSMCs. DISCUSSION: Kv7 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.
INTRODUCTION: Potassium (K(+)) channels are key regulators of vascular smooth muscle cell (VSMC) excitability. In systemic small arteries, Kv7 channel expression/activity has been noted and a role in vascular tone regulation demonstrated. We aimed to demonstrate functional Kv7 channels in human fetoplacental small arteries. METHODS:Human placental chorionic plate arteries (CPAs) were obtained at term. CPA responses to Kv7 channel modulators was determined by wire myography. Presence of Kv7 channel mRNA (encoded by KCNQ1-5) and protein expression were assessed by RT-PCR and immunohistochemistry/immunofluorescence, respectively. RESULTS: Kv7 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 Kv7.1 - Kv7.5 channels. All CPAs assessed expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs. Kv7 protein expression was confirmed in intact CPAs and isolated VSMCs. DISCUSSION: Kv7 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.
Authors: Samuel N Baldwin; Shaun L Sandow; Gema Mondéjar-Parreño; Jennifer B Stott; Iain A Greenwood Journal: Front Physiol Date: 2020-12-07 Impact factor: 4.566
Authors: Christina E Hayward; Samantha Lean; Colin P Sibley; Rebecca L Jones; Mark Wareing; Susan L Greenwood; Mark R Dilworth Journal: Front Physiol Date: 2016-02-05 Impact factor: 4.566