Inhibitory Effect of terpinen-4-ol on Voltage-Dependent Potassium Currents in Rat Small Sensory Neurons

J Nat Prod. 2015 Feb 27;78(2):173-80. doi: 10.1021/np4009249. Epub 2015 Jan 21.

Abstract

The biological and pharmacological activities of the terpenoid terpinen-4-ol (1), which include depressant effects in the central nervous system, are of potential therapeutic interest. In the present study, the effects of 1 on neuronal excitability and voltage-dependent K(+) currents in the somatic sensory system were investigated. Intact and dissociated neurons of rat dorsal root ganglia (DRG) were used for intracellular and patch-clamp recordings, respectively. In neurons of intact DRG, 1 caused concentration-dependent depolarization of the resting membrane potential and increased input resistance. 1 also inhibited action potentials (AP) and decreased AP parameters, with the exception of AP duration, which was increased. In dissociated DRG neurons, 1 partially blocked the total K(+) current in a concentration-dependent manner. 1 inhibited I(A), I(D), and I(K) with IC50 values of 3.2 ± 03, 0.7 ± 0.1, and 1.6 ± 0.7 mM, respectively. 1 did not shift either the steady-state activation or inactivation curves of I(A), I(D), and I(K) but reduced the decay time course of I(A). The alterations in DRG reported here are consistent with the inhibition of K(+) currents and might partially explain the effect of 1 on excitable tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Central Nervous System / drug effects*
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / cytology
  • Male
  • Membrane Potentials / drug effects
  • Molecular Structure
  • Potassium Channel Blockers / pharmacokinetics
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels, Voltage-Gated / physiology*
  • Rats
  • Sensory Receptor Cells / drug effects*
  • Terpenes / chemistry
  • Terpenes / pharmacokinetics
  • Terpenes / pharmacology*

Substances

  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Terpenes
  • terpinenol-4