Kava extract ingredients, (+)-methysticin and (+/-)-kavain inhibit voltage-operated Na(+)-channels in rat CA1 hippocampal neurons

Neuroscience. 1997 Nov;81(2):345-51. doi: 10.1016/s0306-4522(97)00177-2.

Abstract

The action of synthetic kava pyrones, (+)-methysticin and (+/-)-kavain, on voltage-operated Na(+)-channels was studied in whole-cell patch-clamped CA1 hippocampal neurons. In doses of 1-400 microM, both compounds exerted a rapid and reversible inhibition of the peak amplitude of Na(+)-currents. Shifting holding membrane potential (Vhold) to more positive values enhanced their blocking effect. The drugs studied did not demonstrate use-dependent properties at 10 Hz stimulation but shifted H infinity curve toward more negative potentials, accelerated time-course of inactivation and slowed down the recovery from inactivation. Voltage-dependence of Na(+)-channel inhibition can be explained by interaction of (+)-methysticin and (+/-)-kavain with resting closed and inactivated states of Na(+)-channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects*
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology*
  • Pyrans / pharmacology*
  • Pyrones / pharmacology*
  • Rats
  • Rats, Wistar
  • Sodium Channels / drug effects*

Substances

  • Neuroprotective Agents
  • Pyrans
  • Pyrones
  • Sodium Channels
  • methysticin
  • kavain