Eugenol Inhibits K⁺ Currents in Trigeminal Ganglion Neurons

Abstract

Eugenol, a natural capsaicin congener, is widely used in dentistry. Eugenol inhibits voltage-activated Na+ and Ca2+ channels in a transient receptor potential vanilloid 1 (TRPV1)-independent manner. We hypothesized that eugenol also inhibits voltage-gated K+ currents, and investigated this in rat trigeminal ganglion neurons and in a heterologous system using whole-cell patch clamping. Eugenol inhibited voltage-gated K+ currents, and the inhibitory effects of eugenol were observed in both capsaicin-sensitive and capsaicin-insensitive neurons. Pre-treatment with capsazepine, a well-known antagonist of TRPV1, failed to block the inhibitory effects of eugenol on K+ currents, suggesting no involvement of TRPV1. Eugenol inhibited human Kv1.5 currents stably expressed in Ltk− cells, where TRPV1 is not endogenously expressed. We conclude that eugenol inhibits voltage-gated K+ currents in a TRPV1-independent manner. The inhibition of voltage-gated K+ currents is likely to contribute to the irritable action of eugenol. Abbreviations: human Kv1.5 channel, hKv1.5; transient receptor potential vanilloid 1, TRPV1.

Eugenol Inhibits ATP-induced P2X Currents in Trigeminal Ganglion Neurons

“…Eugenol inhibited ATP-induced P2X currents in nociceptive TG neurons in a TRPV1 independent manner, which is consistent with eugenol action on voltage-sensitive channels (Lee et al, 2005;Park et al, 2006;Li et al, 2007;Chung et al, 2008). Inhibition of ATP-induced P2X currents by eugenol was observed in both capsaicin-sensitive and capsaicin-insensitive TG neurons.…”

“…We have recently demonstrated that inhibition of voltage-gated Na ＋ and Ca 2＋ channel currents by eugenol might contribute to its analgesic effects (Lee et al, 2005;Park et al, 2006;Chung et al, 2008). Furthermore, we showed that the activation of TRPV1 and inhibition of voltage-gated K ＋ channel currents might be involved in its stimulatory effects (Yang et al, 2003;Li et al, 2007), and that the inhibitory effects of eugenol on voltage-gated ion channels result from TRPV1 independent mechanisms although eugenol per se activates TRPV1. Given the fact that wide ranges of ion channels are modulated by eugenol, there could be another molecular target for eugenol.…”

Anaesthesia of farmed fish: implications for welfare

“…It is structurally similar to eugenol, a widely used analgesic in dentistry that inhibits sodium, potassium and calcium channels, inhibits NMDA receptors and potentiates GABA A receptors (Aoshima and Hamamoto 1999; Lee et al 2005;Li et al 2007;Park et al 2006;Wie et al 1997). Like eugenol, isoeugenol is one of the constituents of clove oil, another widely used fish anaesthetic.…”

Anesthesia induces stress in Atlantic salmon (Salmo salar), Atlantic cod (Gadus morhua) and Atlantic halibut (Hippoglossus hippoglossus)

“…MS-222 and benzocaine are local anesthetics that inhibit neural signal transmission by blocking voltage sensitive sodium channels (Frazier and Narahashi 1975;Neumcke et al 1981). Isoeugenol is similar to eugenol, a widely used analgesic in dentistry which inhibits sodium, potassium, and calcium channels, inhibits N-methyl-D-aspartate (NMDA) receptors and potentiates inhibitory gamma-aminobutyric acid type A (GABA A ) receptors (Aoshima and Hamamoto 1999;Lee et al 2005;Li et al 2007;Park et al 2006;Wie et al 1997). Metomidate is a methyl analogue of etomidate, a non-barbiturate hypnotic that modulates and activates GABA A receptors (Ashton and Wauquier 1985;Grasshoff et al 2006;Rusch et al 2004;Yang and Uchida 1996).…”