Enhancement of Voltage-Gated K+ Channels and Depression of Voltage-Gated Ca2+ Channels Are Involved in Quercetin-Induced Vasorelaxation in Rat Coronary Artery

Hou, Xiaomin; Liu, Yu; Niu, Longgang; Zhang, Mingsheng

doi:10.1055/s-0034-1368320

Cited by 44 publications

(25 citation statements)

References 44 publications

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“…The study by Hou et al . provides support to the latter observation. Indeed, the QRS complex also was decreased by quercetin indicating that it affected the rate of ventricular depolarization suggesting that quercetin modified voltage‐dependent Na + channels.…”

Section: Discussionsupporting

confidence: 71%

“…Quercetin decreased QTc showing that it accelerated ventricular repolarization, probably by activating voltage-dependent K + channels. The study by Hou et al [34] provides support to the latter observation. Indeed, the QRS complex also was decreased by quercetin indicating that it affected the rate of ventricular depolarization suggesting that quercetin modified voltage-dependent Na + channels.…”

Section: Discussionmentioning

confidence: 70%

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Dissection of the Effects of Quercetin on Mouse Myocardium

Santos

Oliveira

Santos‐Miranda

et al. 2017

Basic Clin Pharma Tox

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Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 μM quercetin increased I at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V ) shifted towards more negative potentials from -13.06 ± 1.52 mV to -19.26 ± 1.72 mV and did not alter the slope factor. Furthermore, quercetin increased [Ca ] transient by 28% when compared to control. Quercetin accelerated [Ca ] transient decay time, which could be attributed to SERCA activation. In resting cardiomyocytes, quercetin did not change amplitude or frequency of Ca sparks. In isolated heart, quercetin increased heart rate and decreased PRi, QTc and duration of the QRS complex. Thus, we showed that quercetin activates β-adrenoceptors, leading to increased L-type Ca current and cell-wide intracellular Ca transient without visible changes in Ca sparks.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 70%

Dissection of the Effects of Quercetin on Mouse Myocardium

Santos

Oliveira

Santos‐Miranda

et al. 2017

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…In other cell types, quercetin has also been reported to act on Ca 2+ -and K + -and channels. It was found to inhibit inward Ca 2+ currents through L-type voltage-gated Ca 2+ channels in coronary arterial smooth muscle cells and to enhance voltage-gated K + channels leading to vasorelaxation [54]. In coronary artery smooth muscle cells quercetin was shown to promote relaxation by stimulation of large-conductance Ca 2+ -activated K + currents [55].…”

Section: Discussionmentioning

confidence: 99%

Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells

Kittl

Beyreis

Tumurkhuu

et al. 2016

Cell Physiol Biochem

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Background/Aims: Previously we described insulinotropic effects of Leonurus sibiricus L. plant extracts used for diabetes mellitus treatment in Traditional Mongolian Medicine. The flavonoid quercetin and its glycoside rutin, which exert anti-diabetic properties in vivo by interfering with insulin signaling in peripheral target tissues, are constituents of these extracts. This study was performed to better understand short- and long-term effects of quercetin and rutin on beta-cells. Methods: Cell viability, apoptosis, phospho-protein abundance and insulin release were determined using resazurin, annexin-V binding assays, Western blot and ELISA, respectively. Membrane potentials (V_mem), whole-cell Ca²⁺ (ICa)- and ATP-sensitive K⁺ (IK_ATP) currents were measured by patch clamp. Intracellular Ca²⁺ (Ca_i) levels were measured by time-lapse imaging using the ratiometric Ca²⁺ indicator Fura-2. Results: Rutin, quercetin and the phosphoinositide-3-kinase (PI3K) inhibitor LY294002 caused a dose-dependent reduction in cell viability with IC₅₀ values of ∼75 µM, ∼25 µM and ∼3.5 µM, respectively. Quercetin (50 µM) significantly increased the percentage of Annexin-V+ cells within 48 hrs. The mean cell volume (MCV) of quercetin-treated cells was significantly lower. Within 2 hrs, quercetin significantly decreased basal- and insulin-stimulated Akt(T308) phosphorylation and increased Erk1/2 phosphorylation, without affecting P-Akt(S473) abundance. Basal- and glucose-stimulated insulin release were significantly stimulated by quercetin. Quercetin significantly depolarized V_mem by ∼25 mV which was prevented by the K_ATP-channel opener diazoxide, but not by the L-type ICa inhibitor nifedipine. Quercetin significantly stimulated ICa and caused a 50% inhibition of IK_ATP. The effects on V_mem, ICa and IK_ATP rapidly reached peak values and then gradually diminished to control values within ∼1 minute. With a similar time-response quercetin induced an elevation in Ca_i which was completely abolished in the absence of Ca²⁺ in the bath solution. Rutin (50 µM) did not significantly alter the percentage of Annexin-V+ cells, MCV, Akt or Erk1/2 phosphorylation, insulin secretion, or the electrophysiological behavior of INS-1 cells. Conclusion: We conclude that quercetin acutely stimulates insulin release, presumably by transient K_ATP channel inhibition and ICa stimulation. Long term application of quercetin inhibits cell proliferation and induces apoptosis, most likely by inhibition of PI3K/Akt signaling.

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“…Naringenin (5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one) has been reported to be a BK Ca channel opener [133]. Hesperetin, the aglycone of hesperidin, and quercetin were reported to inhibit L-type Ca 2+ channels and increase voltage-gated K + channels [134,135]. Moreover, quercetin was found to inhibit Na + channels in hippocampal pyramidal neurons [136].…”

Section: Other Ion Channelsmentioning

confidence: 99%