Eugenol has been used as an
analgesic in dentistry. Previous studies have demonstrated that voltage-gated Na(+) channels and high-voltage-activated Ca(2+) channels expressed in trigeminal ganglion (TG) neurons sensing dental
pain are molecular targets of
eugenol for its
analgesic effects. However, it has not been investigated whether
eugenol can affect T-type Ca(2+) channels, which are known to be detected in the afferent neurons. In this report, we investigate how
eugenol can influence cloned T-type channel
isoforms expressed in HEK293 cells, using whole-cell patch clamp. Application of
eugenol inhibited Cav3.1, Cav3.2, and Cav3.3 currents in a concentration-dependent manner with IC50 values of 463, 486, and 708 μM, respectively.
Eugenol was found to negatively shift the steady-state inactivation curves of the T-type channel
isoforms, but it did not shift their activation curves. In addition,
eugenol had little effect on the current kinetics of Cav3.1 and Cav3.2, but it accelerated the inactivation kinetics of Cav3.3 currents. Reduction of channel availability enhanced
eugenol inhibition sensitivity for Cav3.1 and Cav3.2, but not for Cav3.3. Moreover,
eugenol inhibition of T-type channel
isoforms was found to be use dependent. Finally, we show that the T-type currents recorded from rat TG neurons were inhibited by
eugenol with a similar potency to Cav3.1 and Cav3.2
isoforms. Taken together, our findings suggest that T-type Ca(2+) channels are additional molecular targets for the
pain-relieving effects of
eugenol.