Effects of eugenol on T-type Ca2+ channel isoforms
Haengsoo Seo1, Hai Ying Li, Edward Perez-Reyes
1Department of Life Science and Basic Science Institute for Cell Damage Control, Sogang University, Seoul, Republic of Korea (H.S., H.Y.L., J.-H.L.); and Department of Pharmacology, University of Virginia, Charlottesville, Virginia (E.P.-R.).
The Journal of Pharmacology and Experimental Therapeutics
|September 10, 2013
Summary
Eugenol, a dental analgesic, inhibits T-type calcium channels (Cav3.1, Cav3.2, Cav3.3) in neurons. This study identifies these channels as new molecular targets for eugenol's pain-relieving effects.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Eugenol is a known dental analgesic.
- Its analgesic effects are linked to voltage-gated sodium and high-voltage-activated calcium channels in trigeminal ganglion neurons.
- The impact of eugenol on T-type calcium channels in afferent neurons remained unexplored.
Purpose of the Study:
- To investigate the influence of eugenol on cloned T-type calcium channel isoforms (Cav3.1, Cav3.2, Cav3.3).
- To determine if T-type calcium channels are molecular targets for eugenol's analgesic properties.
Main Methods:
- Whole-cell patch clamp electrophysiology was used to study cloned T-type channel isoforms expressed in HEK293 cells.
- T-type currents from rat trigeminal ganglion neurons were also recorded and analyzed.
Main Results:
- Eugenol inhibited Cav3.1, Cav3.2, and Cav3.3 currents in a concentration-dependent manner (IC50 values: 463, 486, and 708 μM, respectively).
- Eugenol negatively shifted steady-state inactivation curves but not activation curves of T-type channels.
- Eugenol accelerated Cav3.3 inactivation kinetics and showed use-dependent inhibition, with similar potency observed in rat trigeminal ganglion neurons.
Conclusions:
- T-type calcium channels (Cav3.1, Cav3.2, Cav3.3) are identified as novel molecular targets of eugenol.
- These findings provide a deeper understanding of eugenol's analgesic mechanisms in dental pain.
- Eugenol's interaction with T-type channels contributes to its pain-relieving effects.
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