Resveratrol inhibits Na+ currents in rat dorsal root ganglion neurons.
Resveratrol, a phytoalexin found in grapevines, exerts neuroprotective, cancer chemopreventive, antiinflammatory and cardioprotective activities. Studies have also shown that resveratrol exhibits analgesic effects. Cyclooxygenase inhibition and K+ channel opening have been suggested as underlying mechanisms for the resveratrol-induced analgesia. Here, we investigated the effects of resveratrol on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na+ currents in rat dorsal root ganglion (DRG) neurons. Resveratrol suppressed both Na+ currents evoked at 0 mV from -80 mV. TTX-S Na+ current (K(d), 72 microM) was more susceptible to resveratrol than TTX-R Na+ current (K(d), 211 microM). Although the activation voltage of TTX-S Na+ current was shifted in the depolarizing direction by resveratrol, that of TTX-R Na+ current was not. Resveratrol caused a hyperpolarizing shift of the steady-state inactivation voltage and slowed the recovery from inactivation of both Na+ currents. However, no frequency-dependent inhibition of resveratrol on either type of Na+ current was observed. The suppression and the unfavorable effects on the kinetics of Na+ currents in terms of the excitability of DRG neurons may make a great contribution to the analgesia by resveratrol.
Kim
Hong Im
HI
Department of Pharmacology, Chung-Ang University, College of Medicine, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756, Republic of Korea.
Kim
Tae Hoon
TH
Song
Jin-Ho
JH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D000077185:Resveratrol; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C503480:Scn9a protein, rat; D015222:Sodium Channels; D013267:Stilbenes; D000077185:Resveratrol