title: Tungstate activates BK channels in a β subunit- and Mg2+-dependent manner: relevance for arterial vasodilatation.
abstract: OBJECTIVE
  Tungstate reduces blood pressure in experimental animal models of both hypertension and metabolic syndrome, although the underlying mechanisms are not fully understood. Given that the large-conductance voltage- and Ca(2+)-dependent K(+) (BK) channel is a key element in the control of arterial tone, our aim was to evaluate whether BK channel modulation by tungstate can contribute to its antihypertensive effect.
  
  
  RESULTS
  Patch-clamp studies of heterologously expressed human BK channels (α + β(1-4) subunits) revealed that cytosolic tungstate (1 mM) induced a significant left shift (∼20 mV) in the voltage-dependent activation curve only in BK channels containing αβ(1) or αβ(4) subunits, but reduced the amplitude of K(+) currents through all BK channels tested. The β(1)-dependent activation of BK channels by tungstate was enhanced at cytosolic Ca(2+) levels reached during myocyte contraction, and prevented either by removal of cytosolic Mg(2+) or by mutations rendering the channel insensitive to Mg(2+). A lower concentration of tungstate (0.1 mM) induced voltage-dependent activation of the vascular BKαβ(1) channel without reducing current amplitude, and consistently exerted a vasodilatory action on wild-type but not on β(1)-knockout mouse arteries pre-contracted with endothelin-1.
  
  
  CONCLUSIONS
  Tungstate activates BK channels in a β subunit- and Mg(2+)-dependent manner and induces vasodilatation only in mouse arteries that express the BK β(1) subunit.
authors.affiliation: Laboratori de Fisiologia Molecular i Canalopaties, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, Barcelona, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Fernández-Mariño
authors.forename: Cristina
authors.initials: C
authors.lastname: Porras-González
authors.forename: Patricia
authors.initials: P
authors.lastname: González-Rodríguez
authors.forename: Jana
authors.initials: J
authors.lastname: Selent
authors.forename: Manuel
authors.initials: M
authors.lastname: Pastor
authors.forename: Juan
authors.initials: J
authors.lastname: Ureña
authors.forename: Antonio
authors.initials: A
authors.lastname: Castellano
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valverde
authors.forename: José M
authors.initials: JM
authors.lastname: Fernández-Fernández
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000187:drug effects*; D008274:Magnesium / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017973:Tungsten Compounds / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D017973:Tungsten Compounds; D008274:Magnesium; C045951:tungstate