Please use this identifier to cite or link to this item:
|Statistics||SHARE CORE MendeleyBASE||
|Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE|
Tungstate activates BK channels in a β subunit-and Mg 2+-dependent manner: Relevance for arterial vasodilatation
|Authors:||Fernández-Maríño, A. I.; Porras-González, Cristina; González-Rodríguez, P.; Selent, J.; Pastor, Manuel; Ureña, Juan; Castellano, Antonio; Valverde, M. A.; Fernández-Fernández, J. M.|
|Publisher:||European Society of Cardiology|
|Citation:||Cardiovascular Research 95(1): 29-38 (2012)|
|Abstract:||Aims: 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.|
Methods and 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 β1-knockout mouse arteries pre-contracted with endothelin-1.
Conclusion: 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. Published on behalf of the European Society of Cardiology. All rights reserved. © 2012 The Author.
|Appears in Collections:||(IBIS) Artículos|