| First Author | Fernández-Mariño AI | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 95 |
| Issue | 1 | Pages | 29-38 |
| PubMed ID | 22473360 | Mgi Jnum | J:202579 |
| Mgi Id | MGI:5520036 | Doi | 10.1093/cvr/cvs139 |
| Citation | Fernandez-Marino AI, et al. (2012) Tungstate activates BK channels in a beta subunit- and Mg2+-dependent manner: relevance for arterial vasodilatation. Cardiovasc Res 95(1):29-38 |
| abstractText | 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 (alpha + beta(1-4) subunits) revealed that cytosolic tungstate (1 mM) induced a significant left shift ( approximately 20 mV) in the voltage-dependent activation curve only in BK channels containing alphabeta(1) or alphabeta(4) subunits, but reduced the amplitude of K(+) currents through all BK channels tested. The beta(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 BKalphabeta(1) channel without reducing current amplitude, and consistently exerted a vasodilatory action on wild-type but not on beta(1)-knockout mouse arteries pre-contracted with endothelin-1. CONCLUSION: Tungstate activates BK channels in a beta subunit- and Mg(2+)-dependent manner and induces vasodilatation only in mouse arteries that express the BK beta(1) subunit. |
