Abstract
BackgroundResveratrol, a phytoalexin found in grapes and red wine, exhibits diverse pharmacological activities. However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. The large-conductance calcium-activated potassium channels (BKCa) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. The present study aimed to determine the effects of resveratrol on BKCa currents and voltage-gated sodium currents in cortical neurons.ResultsResveratrol concentration-dependently increased the current amplitude and the opening activity of BKCa channels, but suppressed the amplitude of voltage-gated sodium currents. Similar to the BKCa channel opener NS1619, resveratrol decreased the firing rate of action potentials. In addition, the enhancing effects of BKCa channel blockers tetraethylammonium (TEA) and paxilline on action potential firing were sensitive to resveratrol. Our results indicated that the attenuation of action potential firing rate by resveratrol might be mediated through opening the BKCa channels and closing the voltage-gated sodium channels.ConclusionsAs BKCa channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol.
Highlights
Resveratrol, a phytoalexin found in grapes and red wine, exhibits diverse pharmacological activities
The action potential firing rates evoked by the depolarizing current and large-conductance calcium-activated potassium channel (BKCa) channel blockers were remarkably decreased by application of resveratrol. These results suggest that alterations of BKCa channel activity and sodium currents by resveratrol may contribute to its reducing effect on action potential firing rates of cortical neurons
To evaluate whether resveratrol could affect the BKCa currents in cortical neurons, the effects of resveratrol on the current amplitude were examined in the presence of TEA, a BKCa channel blocker
Summary
Resveratrol, a phytoalexin found in grapes and red wine, exhibits diverse pharmacological activities. Relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. The large-conductance calcium-activated potassium channels (BKCa) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. The present study aimed to determine the effects of resveratrol on BKCa currents and voltage-gated sodium currents in cortical neurons. Resveratrol has been reported to regulate ion channel activities in a variety of cells. Voltage-gated sodium channels in cardiomyocytes [47] and rat dorsal root ganglion neurons [21] are blocked by resveratrol. Resveratrol stimulates BKCa channels in vascular endothelial cells [24] and human cardiac fibroblasts [51]
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