| First Author | Scornik FS | Year | 2013 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 304 |
| Issue | 11 | Pages | H1471-82 |
| PubMed ID | 23542916 | Mgi Jnum | J:198209 |
| Mgi Id | MGI:5495860 | Doi | 10.1152/ajpheart.00939.2012 |
| Citation | Scornik FS, et al. (2013) DiBAC4(3) hits a "sweet spot" for the activation of arterial large-conductance Ca2+-activated potassium channels independently of the beta1-subunit. Am J Physiol Heart Circ Physiol 304(11):H1471-82 |
| abstractText | The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)] has been reported as a novel large-conductance Ca(2+)-activated K(+) (BK) channel activator with selectivity for its beta1- or beta4-subunits. In arterial smooth muscle, BK channels are formed by a pore-forming alpha-subunit and a smooth muscle-abundant regulatory beta1-subunit. This tissue specificity has driven extensive pharmacological research aimed at regulating arterial tone. Using animals with a disruption of the gene for the beta1-subunit, we explored the effects of DiBAC4(3) in native channels from arterial smooth muscle. We tested the hypothesis that, in native BK channels, activation by DiBAC4(3) relies mostly on its alpha-subunit. We studied BK channels from wild-type and transgenic beta1-knockout mice in excised patches. BK channels from brain arteries, with or without the beta1-subunit, were similarly activated by DiBAC4(3). In addition, we found that saturating concentrations of DiBAC4(3) ( approximately 30 muM) promote an unprecedented persistent activation of the channel that negatively shifts its voltage dependence by as much as -300 mV. This "sweet spot" for persistent activation is independent of Ca(2+) and/or the beta1-4-subunits and is fully achieved when DiBAC4(3) is applied to the intracellular side of the channel. Arterial BK channel response to DiBAC4(3) varies across species and/or vascular beds. DiBAC4(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. |
