Quercetin is one of the most common flavonoids in the human daily diet. Its affects the coronary artery, especially L-type voltage-gated Ca²⁺ channels and voltage-gated K⁺ channels in the arterial smooth muscle cells, which are poorly understood. The present experiments were designed to study the myogenic effect of quercetin and its possible underlying mechanisms in the rat coronary artery. A wire myograph was used to observe the myogenic effects. Arterial smooth muscle cells were freshly isolated from the rat coronary artery and the intracellular free Ca²⁺ concentration was measured with molecular probe fluo-4-AM. The effects of quercetin on L-type voltage-gated Ca²⁺ channels and voltage-gated K⁺ channels were studied using a whole-cell patch clamp. Quercetin (3–30 µM) produced a depression and relaxation on the contraction induced by KCl or the thromboxane A2 analog 9,11-Dideoxy-9α,11α-methanoepoxy prostaglandin F _2α . The vasorelaxation was attenuated by 4-aminopyridine, a specific voltage-gated K⁺ channel inhibitor, but was not affected by the NG-nitro-L-arginine methylester ester (a nitric oxide synthesis inhibitor), glibenclamide (a ATP-activated K⁺ channel inhibitor), iberiotoxin (a Ca²⁺-activated K⁺ channel inhibitor), BaCl₂ (an inward rectifier K⁺ channel inhibitor), or by endothelium denudation. At the same concentrations, quercetin reduced the KCl-induced elevation of the intracellular free Ca²⁺ concentration, inhibited the inward Ca²⁺ currents through L-type voltage-gated Ca²⁺ channels, and increased the outward K⁺ currents through voltage-gated K⁺ channels in the rat coronary artery smooth muscle cells. Collectively, our results demonstrate that quercetin possesses vasospasmolytic effects in RCA and suggest that depression of the Ca²⁺ influx through L-type voltage-gated Ca²⁺ channels and augmentation of voltage-gated K⁺ channel activity in the myocytes may underlie coronary relaxation.

Dopamine (DA) has a vital role in the central nervous system and also modulates lipid and glucose metabolism. The present study aimed to investigate the effect of dopamine on insulin secretion and the underlying mechanisms in rat pancreatic β-cells. Data from the radioimmunoassay indicated that dopamine inhibited insulin secretion in a glucose- and dose-dependent manner. This inhibitory effect of dopamine was mediated mainly by D2-like receptors, but not D1-like receptors. Whole-cell patch-clamp recordings showed that dopamine decreased voltage-dependent Ca²⁺ channel currents, which could be reversed by inhibition of the D2-like receptor. Dopamine increased voltage-dependent potassium (K_V) channel currents and shortened action potential duration, which was antagonized by inhibition of D2-like receptors. Further experiments showed that D2-like receptor activation by quinpirole increased K_V channel currents. In addition, using calcium imaging techniques, we found that dopamine reduced intracellular Ca²⁺ concentration, which was also reversed by D2-like receptor antagonists. Similarly, quinpirole was found to decrease intracellular Ca²⁺ levels. Taken together, these findings demonstrate that dopamine inhibits insulin secretion mainly by acting on D2-like receptors, inhibiting Ca²⁺ channels, and activating Kv channels. This process results in shortened action potential duration and decreased intracellular Ca²⁺ levels in β-cells. This work offers new insights into a glucose-dependent mechanism whereby dopamine regulates insulin secretion.