The effects of myricetin (3,3’,4’,5,5’,7-hesahydroxyflavone), a natural flavonoid found in edible plants, were studied on vascular smooth muscle L-type Ca2+ channels by comparing its mechanical, radioligand binding, and electrophysiological properties to those of the Ca2+ channel agonist (S)-(-)-Bay K 8644.
In rat aorta rings, both myricetin and (S)-(-)-Bay K 8644 induced contractile responses, which were dependent upon prior exposure to K+. At 15 mM K+ (K15) the pEC50 values for myricetin and (S)-(-)-Bay K 8644 were 4.43±0.03 and 7.92±0.13, respectively. Furthermore, the maximum tension response to myricetin was not significantly different from that elicited by either (S)-(-)-Bay K 8644 or K60. The Ca2+ channel blockers nifedipine, verapamil and diltiazem antagonised and fully reverted myricetin-, (S)-(-)-Bay K 8644- as well as K60-induced contractions. Both myricetin and (S)-(-)-Bay K 8644 potentiated rat aorta ring responses to K+, shifting the K+ concentration-response curve to the left. (S)-(-)-Bay K 8644, but not myricetin, inhibited in a concentration-dependent manner (+)-[3H]PN200–110 binding in porcine aortic membranes. Electrophysiological recordings from single rat tail artery myocytes, under amphotericin B-perforated as well as conventional methods, showed that both myricetin and (S)-(-)-Bay K 8644 increased L-type Ba2+ current (IBa(L)) and shifted the maximum of the current-voltage relationship by 10 mV in the hyperpolarising direction, without, however, modifying the threshold potential. Furthermore, (S)-(-)-Bay K 8644 accelerated both activation and inactivation kinetics of IBa(L) while myricetin slowed down the activation kinetics. Finally, both (S)-(-)-Bay K 8644 and myricetin slowed down deactivation kinetics of IBa(L).
These results suggest that myricetin induces vasoconstriction by activating L-type Ca2+ channel with similar efficacy but a site of action different to that of (S)-(-)-Bay K 8644.
(S)-(-)-Bay K 8644MyricetinVascular smooth muscleWhole-cell patch-clampWine polyphenols