The effects of quercetin, a natural polyphenolic compound, on voltage-dependent L-type Ca2+ current (ICa,L) in rat pituitary GH3 cells were investigated with the aid of the whole-cell voltage-camp technique. Quercetin (0.5-200 μM) stimulated ICa,L in a concentration-dependent manner. The current-voltage (I-V) relationship of ICa,L was slightly shifted to more negative potentials in the presence of quercetin. The EC50 value of the quercetin-induced stimulation of ICa,L was about 7 μM. The presence of quercetin (5 μM) shifted the steady state inactivation curve of ICa,L to a more negative potential by approximately -10 mV. Although quercetin might increase intracellular cyclic AMP, sp-cAMPS did not affect ICa,L. In addition, neither flavone nor wortmannin had any effect on the amplitude of ICa,L, while epicatechin and genistein slightly suppressed it. Quercetin (50 μM) decreased the amplitude of tetrodotoxin-sensitive Na+ current in GH3 cells. Under current-clamp configuration, quercetin could increase the firing frequency of actions potentials. Conversely, in NG108-15 neuronal cells, quercetin suppressed the amplitude of ICa,L. The quercetin-induced inhibition of ICa,L was abolished in NG108-15 cells preincubated with t-butyl hydroperoxide (1 mM). Quercetin-mediated stimulation of ICa,L in GH3 cells was presumably not associated with the level of intracellular cyclic AMP, or with the activity of tyrosine or phosphoinositide 3-kinases. Therefore, the effects of quercetin on ion currents may, at least in part, contribute to the underlying mechanisms through which it affects neuronal or neuroendocrine function.
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