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 (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.