Effects of eugenol on T-type Ca2+ channel isoforms.

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.
AuthorsHaengsoo Seo, Hai Ying Li, Edward Perez-Reyes, Jung-Ha Lee
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 347 Issue 2 Pg. 310-7 (Nov 2013) ISSN: 1521-0103 [Electronic] United States
PMID24014106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Analgesics
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Protein Isoforms
  • Eugenol
  • Analgesics (pharmacology)
  • Calcium Channel Blockers (pharmacology)
  • Calcium Channels, T-Type (genetics, metabolism)
  • Eugenol (pharmacology)
  • HEK293 Cells
  • Humans
  • Kinetics
  • Membrane Potentials (drug effects)
  • Neurons, Afferent (cytology, drug effects, metabolism)
  • Patch-Clamp Techniques
  • Protein Binding
  • Protein Isoforms
  • Transfection
  • Trigeminal Ganglion (cytology, drug effects, metabolism)

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