title: Resveratrol attenuates cortical neuron activity: roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels.
abstract: BACKGROUND
  Resveratrol, 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.
  
  
  RESULTS
  Resveratrol 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.
  
  
  CONCLUSIONS
  As 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.
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, 35, Keyan Road, Zhunan, Miaoli County, 35053, Taiwan.
authors.forename: Ya-Jean
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, National Chengchi University, 64, Sec.2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan.|Research Center for Mind, Brain, and Learning, National Chengchi University, 64, Sec.2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan.
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan.
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology, National Cheng Kung University Medical College, 1 University Road, Tainan City, 70101, Taiwan. snwu@mail.ncku.edu.tw.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wu
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, 35, Keyan Road, Zhunan, Miaoli County, 35053, Taiwan. hwei@nhri.org.tw.|Institute of Neuroscience, National Chengchi University, 64, Sec.2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan. hwei@nhri.org.tw.|Department of Pharmacology and Toxicology, School of Medicine, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan. hwei@nhri.org.tw.
authors.forename: Hwei-Hisen
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D001562:Benzimidazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D013267:Stilbenes; D061566:Voltage-Gated Sodium Channels; C086491:NS 1619; D000077185:Resveratrol
keywords: Action potential; BKCa channel; Firing rate; Resveratrol; Sodium channel