Quercetin relaxes rat tail main artery partly via a PKG‐mediated stimulation of KCa1.1 channels. (25th March 2013)

• Record Type: Journal Article
• Authors: Iozzi, D.; Schubert, R.; Kalenchuk, V. U.; Neri, A.; Sgaragli, G.; Fusi, F.; Saponara, S.
• Is Part Of: Acta physiologica. Volume 208:Number 4(2013:Aug.)
• Page Start: 329
• Page End: 339
• Publication Date: 2013-03-25
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12083
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" xml:lang="en" id="apha12083-abs-0001"> <title>Abstract</title> <sec id="apha12083-sec-0001" sec-type="section"> <title>Aim</title> <p>Protein kinases, activated by vasodilator substances, affect vascular function by regulating large conductance Ca<sup>2+</sup>‐activated K<sup>+</sup> (K<sub>Ca</sub>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<sub>Ca</sub>1.1 currents.</p> </sec> <sec id="apha12083-sec-0002" sec-type="section"> <title>Methods</title> <p>Single freshly isolated myocytes and endothelium‐denuded rings of the rat tail main artery were employed for electrophysiological and contractility measurements respectively.</p> </sec> <sec id="apha12083-sec-0003" sec-type="section"> <title>Results</title> <p>Quercetin relaxed vessels and increased K<sub>Ca</sub>1.1 currents in a concentration‐dependent manner: both effects were antagonized by the specific K<sub>Ca</sub>1.1 channel blocker iberiotoxin. Stimulation of K<sub>Ca</sub>1.1 currents was fully reversible upon drug washout, markedly reduced by Rp‐8‐Br‐PET‐cGMPs, a PKG‐inhibitor, but not affected by catalase. Quercetin shifted by 34.3 mV the voltage dependence of K<sub>Ca</sub>1.1 channel activation towards more negative membrane potentials without affecting its slope. Under conditions of tight functional coupling between sarcoplasmic reticulum Ca<sup>2+</sup> release sites and K<sub>Ca</sub>1.1 channels, quercetin decreased both the frequency and the amplitude of K<sub>Ca</sub>1.1 transient currents in a ryanodine‐like manner.</p> </sec> <sec id="apha12083-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The natural flavonoid quercetin relaxes the rat tail main artery partly <italic>via</italic> a PKG‐mediated stimulation of smooth muscle K<sub>C</sub><sub>a</sub>1.1 channels.</p> </sec> </abstract>