Quercetin antagonism of Bay K 8644 effects on rat tail artery L-type Ca(2+) channels.
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.
Saponara
Simona
S
Dipartimento di Neuroscienze, Sezione di Farmacologia, Fisiologia e Tossicologia, Università degli Studi di Siena, via A. Moro 2, Siena, Italy. saponara@unisi.it
Sgaragli
Giampietro
G
Fusi
Fabio
F
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D019789:Tetraethylammonium / Q000494:pharmacology
D000975:Antioxidants; D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011794:Quercetin