title: Quercetin relaxes rat tail main artery partly via a PKG-mediated stimulation of KCa 1.1 channels.
abstract: OBJECTIVE
  Protein kinases, activated by vasodilator substances, affect vascular function by regulating large conductance Ca(2+) -activated K(+) (KCa 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 KCa 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 KCa 1.1 currents in a concentration-dependent manner: both effects were antagonized by the specific KCa 1.1 channel blocker iberiotoxin. Stimulation of KCa 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 KCa 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 KCa 1.1 channels, quercetin decreased both the frequency and the amplitude of KCa 1.1 transient currents in a ryanodine-like manner.
  
  
  CONCLUSIONS
  The natural flavonoid quercetin relaxes the rat tail main artery partly via a PKG-mediated stimulation of smooth muscle KC a 1.1 channels.
authors: Dipartimento di Scienze della Vita, Università degli Studi di Siena, Siena, Italy.
authors: D
authors: D
authors: Iozzi
authors: R
authors: R
authors: Schubert
authors: V U
authors: VU
authors: Kalenchuk
authors: A
authors: A
authors: Neri
authors: G
authors: G
authors: Sgaragli
authors: F
authors: F
authors: Fusi
authors: S
authors: S
authors: Saponara
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D013623:Tail / Q000098:blood supply*; D013873:Thionucleotides
chemical_list: D000975:Antioxidants; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D013873:Thionucleotides; C098740:8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate; D011794:Quercetin; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP
keywords: large conductance Ca2+-activated K+ channels; quercetin; rat tail main artery myocyte; spontaneous transient outward currents; whole-cell patch-clamp