Eugenol activates Ca(2+)-permeable currents in rat dorsal root ganglion cells

Although little is known about the mechanism of action of eugenol, some related compounds have been compared with capsaicin derivatives in terms of the relationship between their chemical structure and activity. To elucidate whether eugenol and capsaicin act via a common mechanism at the neuronal membrane, we investigated the effects of eugenol on rat DRG neurons using the whole-cell patch-clamp technique. Eugenol (0.125-1 mmol/L) produced an inward current in a concentration-dependent manner. The reversal potential for this inward current was around 0 mV in PSS. In Na(+)-deficient solutions, the amplitude of the inward current was slightly reduced at negative holding potentials, whereas in Ca(2+)-free solution, it was markedly reduced at all holding potentials tested. The reversal potential was not changed by superfusion with either solution. Niflumic acid (100 mumol/L) produced a significant inhibition of the current without a change in the reversal potential. These results suggest that eugenol activates a Ca(2+)-permeable channel as well as a Cl- channel. The latter channel may have been activated by the increase in intracellular Ca2+ concentration caused by the activation of the Ca(2+)-permeable channel. Capsazepine (10 mumol/L) partially inhibited the eugenol-induced current and completely inhibited the capsaicin-induced current. Eugenol (1 mmol/L) produced an inward current even after occurrence of desensitization of the capsaicin-induced current had occurred. Our results suggest that eugenol activates a Ca(2+)-permeable ion channel in rat DRG neurons through two different mechanisms: a capsaicin receptor-mediated pathway and a pathway independent of the capsaicin-receptor.