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

The biological and pharmacological activities of the terpenoid terpinen-4-ol (<b>1</b>), which include depressant effects in the central nervous system, are of potential therapeutic interest. In the present study, the effects of <b>1</b> 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, <b>1</b> caused concentration-dependent depolarization of the resting membrane potential and increased input resistance. <b>1</b> also inhibited action potentials (AP) and decreased AP parameters, with the exception of AP duration, which was increased. In dissociated DRG neurons, <b>1</b> partially blocked the total K⁺ current in a concentration-dependent manner. <b>1</b> inhibited <i>I</i>_A, <i>I</i>_D, and <i>I</i>_K with IC₅₀ values of 3.2 ± 03, 0.7 ± 0.1, and 1.6 ± 0.7 mM, respectively. <b>1</b> did not shift either the steady-state activation or inactivation curves of <i>I</i>_A, <i>I</i>_D, and <i>I</i>_K but reduced the decay time course of <i>I</i>_A. The alterations in DRG reported here are consistent with the inhibition of K⁺ currents and might partially explain the effect of <b>1</b> on excitable tissues