Ana I Fernández-Mariño, Cristina Porras-González, Patricia González-Rodríguez, Jana Selent, Manuel Pastor, Juan Ureña, Antonio Castellano, Miguel A Valverde, José M Fernández-Fernández
Laboratori de Fisiologia Molecular i Canalopaties, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, Barcelona, Spain.
Cardiovascular research 2012 Jul 1Tungstate 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. 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. 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.
Ana I Fernández-Mariño, Cristina Porras-González, Patricia González-Rodríguez, Jana Selent, Manuel Pastor, Juan Ureña, Antonio Castellano, Miguel A Valverde, José M Fernández-Fernández. Tungstate activates BK channels in a β subunit- and Mg2+-dependent manner: relevance for arterial vasodilatation. Cardiovascular research. 2012 Jul 1;95(1):29-38
PMID: 22473360
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