Trans-resveratrol, a red wine ingredient, inhibits voltage-activated potassium currents in rat hippocampal neurons.
The red wine ingredient trans-resveratrol was found to exert potent neuroprotective effects in different in vivo and in vitro models. Thus far, the mechanisms underlying the neuroprotection were attributed mainly to its antioxidant properties. The aim of this study was to investigate the actions of trans-resveratrol on voltage-gated K(+) channels, which have been implicated in neuronal apoptosis. Superfusion of trans-resveratrol reversibly inhibited both the delayed rectifier (I(K)) and fast transient K(+) current (I(A)) in rat dissociated hippocampal neurons with IC(50) values of 13.6 +/- 1.0 microM and 45.7 +/- 7.5 microM, respectively. The inhibition on I(K) had a slow onset, was neither voltage dependent nor use dependent. Trans-resveratrol (30 microM) shifted the steady-state inactivation curve of I(K) to the hyperpolarizing direction by 20 mV and slowed down its recovery from inactivation. The inhibition on I(A) was similar to that on I(K), but voltage dependent. Superfusion of trans-resveratrol (30 microM) shifted the steady-state activation curve of I(A) to the depolarizing direction by 17 mV. Intracellular application of trans-resveratrol (30 microM) was ineffective. Based on the comparable effective concentrations, the inhibition of voltage-activated K(+) currents by trans-resveratrol may contribute to its neuroprotective effects.
Gao
Zhao-Bing
ZB
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China.
Hu
Guo-Yuan
GY
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D024642:Potassium Channels, Voltage-Gated; D013267:Stilbenes; D000077185:Resveratrol