title: Activation of KV7 channels stimulates vasodilatation of human placental chorionic plate arteries.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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: 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.
authors: T A
authors: TA
authors: Mills
authors: 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.
authors: S L
authors: SL
authors: Greenwood
authors: 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.
authors: G
authors: G
authors: Devlin
authors: 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.
authors: Y
authors: Y
authors: Shweikh
authors: 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.
authors: M
authors: M
authors: Robinson
authors: 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.
authors: E
authors: E
authors: Cowley
authors: 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.
authors: C E
authors: CE
authors: Hayward
authors: 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.
authors: E C
authors: EC
authors: Cottrell
authors: 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.
authors: T
authors: T
authors: Tropea
authors: 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.
authors: M F
authors: MF
authors: Brereton
authors: Pcovery Aps, Thorvaldsensvej 57, DK-1871 Frederiksberg C, Denmark. Electronic address: wdalbybrown@gmail.com.
authors: W
authors: W
authors: Dalby-Brown
authors: 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.
authors: M
authors: M
authors: Wareing
mesh_terms: D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D010920:Placenta / Q000098:blood supply*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D007211:Indoles; D051656:KCNQ Potassium Channels; D026902:Potassium Channel Blockers; D011725:Pyridines; C061017:linopirdine
keywords: Human; Placenta; Potassium channel