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Quercetin relaxes rat tail main artery partly via a PKG ‐mediated stimulation of K Ca 1.1 channels
Author(s) -
Iozzi D.,
Schubert R.,
Kalenchuk V. U.,
Neri A.,
Sgaragli G.,
Fusi F.,
Saponara S.
Publication year - 2013
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12083
Subject(s) - iberiotoxin , stimulation , chemistry , ryanodine receptor , biophysics , contractility , medicine , channel blocker , quercetin , cyclopiazonic acid , vasodilation , endoplasmic reticulum , calcium , biology , biochemistry , antioxidant
Aim Protein kinases, activated by vasodilator substances, affect vascular function by regulating large conductance Ca 2+ ‐activated K + ( K Ca 1.1) channels. Thus, the aim of the present investigation was to address the hypothesis that quercetin‐induced vasorelaxation is caused by a PKG ‐mediated stimulation of K Ca 1.1 currents. Methods Single freshly isolated myocytes and endothelium‐denuded rings of the rat tail main artery were employed for electrophysiological and contractility measurements respectively. Results Quercetin relaxed vessels and increased K Ca 1.1 currents in a concentration‐dependent manner: both effects were antagonized by the specific K Ca 1.1 channel blocker iberiotoxin. Stimulation of K Ca 1.1 currents was fully reversible upon drug washout, markedly reduced by Rp‐8‐Br‐ PET ‐ cGMP s, a PKG ‐inhibitor, but not affected by catalase. Quercetin shifted by 34.3 mV the voltage dependence of K Ca 1.1 channel activation towards more negative membrane potentials without affecting its slope. Under conditions of tight functional coupling between sarcoplasmic reticulum Ca 2+ release sites and K Ca 1.1 channels, quercetin decreased both the frequency and the amplitude of K Ca 1.1 transient currents in a ryanodine‐like manner. Conclusion The natural flavonoid quercetin relaxes the rat tail main artery partly via a PKG ‐mediated stimulation of smooth muscle K C a 1.1 channels.