The functional interaction between two L-type Ca(2+) channel activators, quercetin and (S)-(-)-methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate (Bay K 8644), has been investigated in vascular smooth muscle cells. L-type Ca(2+) currents [I(Ca(L))] were recorded in freshly isolated rat tail main artery myocytes using the whole-cell patch-clamp method. Bay K 8644 increased I(Ca(L)) in a concentration-dependent manner with a pEC(50) value of 8.25. Pre-incubation of myocytes with concentrations of quercetin per se ineffective as an L-type Ca(2+) channel activator (0.1 and 0.3 microM) inhibited significantly the maximal response evoked by Bay K 8644, but left unaltered its potency. Quercetin (0.1 microM) prevented the hyperpolarizing shift of the steady-state inactivation curve induced by 0.1 microM Bay K 8644 and its stimulation of I(Ca(L)) tail current intensity without modifying Bay K 8644-induced effects on I(Ca(L)) activation, inactivation, deactivation kinetics as well as on use-dependence and recovery from inactivation. Quercetin at nutritionally meaningful concentrations, limited the responsiveness of vascular L-type Ca(2+) channels to the pharmacological stimulation operated by Bay K 8644. These data contribute to a better understanding of quercetin effects on experimental in vivo cardioprotection.