Original Article

Effects of α₂-adrenoceptor agonists on tetrodotoxin-resistant Na⁺ channels in rat dorsal root ganglion neurons*

A. Oda^a1, H. Iida^a1 c1, S. Tanahashi^a1, Y. Osawa^a1, S. Yamaguchi^a1 and S. Dohi^a1

^a1 Gifu University Graduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu, Japan

Summary

Background and objective When intrathecally or epidurally administered, α₂-adrenoceptor agonists produce potent antinociception by affecting the activity of primary afferent fibres and spinal cord neurons. Recent reports have indicated that in dorsal root ganglion neurons, tetrodotoxin-resistant Na⁺ channels play important roles in the conduction of nociceptive sensation. We therefore investigated the effects of α₂-adrenoceptor agonists on tetrodotoxin-resistant Na⁺ currents.

Methods Using the whole-cell patch-clamp technique, we recorded tetrodotoxin-resistant Na⁺ currents from rat dorsal root ganglion neurons.

Results Both clonidine and dexmedetomidine reduced the peak amplitude of the tetrodotoxin-resistant Na⁺ current concentration- and use-dependently. The concentration required for a half-maximal effect was significantly lower for dexmedetomidine (58.0 ± 10.2 μmol) than for clonidine (257.2 ± 30.9 μmol) at holding potential −70 mV. The current inhibitions induced by these agonists were not prevented by 1 μmol yohimbine, an α₂-adrenoceptor antagonist. Both clonidine and dexmedetomidine shifted the inactivation curve for the tetrodotoxin-resistant Na⁺ current in the hyperpolarizing direction. The combinations clonidine with lidocaine and dexmedetomidine with lidocaine produced an additive blockade-type interaction on the tetrodotoxin-resistant Na⁺ current.

Conclusions The results suggest that a direct inhibition of tetrodotoxin-resistant Na⁺ channels may contribute to the antinociceptive effects of clonidine and dexmedetomidine when used as additives to regional anaesthesia.

(Accepted March 09 2007)

Keywords

• ION CHANNELS;
• SODIUM CHANNELS;
• ANAESTHESIA GENERAL, mechanism of actions of anaesthetics;
• ADRENERGIC ALPHA AGONISTS, dexmedetomidine, clonidine

Correspondence:

^c1 Correspondence to: Hiroki Iida, Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. E-mail: iida@cc.gifu-u.ac.jp; Tel: +81 58 230 6404; Fax: +81 58 230 6405

Footnotes

* Presented in part at the annual meeting of the International Anesthesia Research Society, Ft. Lauderdale, Florida, USA (2001).