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J. Biol. Chem., Vol. 281, Issue 39, 29002-29010, September 29, 2006

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Voltage-gated Sodium Channels Confer Excitability to Human Odontoblasts

POSSIBLE ROLE IN TOOTH PAIN TRANSMISSION^*

Bruno Allard¹, Henry Magloire^¶||12, Marie Lise Couble^¶||, Jean Christophe Maurin^¶||, and Françoise Bleicher^¶||

From the University of Lyon 1, Physiologie Intégrative, Cellulaire et Moléculaire, Villeurbanne F-69100, the UMR CNRS 5123, Villeurbanne F-69100, the ^¶University of Lyon 1, EA 1892-IFR 62, Développement et Régénération des Tissus Dentaires, Faculté d'Odontologie, Lyon F-69008, and the ^||INSERM/ERI 16, Lyon F-69008, France

Odontoblasts are responsible for the dentin formation. They are suspected to play a role in tooth pain transmission as sensor cells because of their close relationship with nerve, but this role has never been evidenced. We demonstrate here that human odontoblasts in vitro produce voltage-gated tetrodotoxin-sensitive Na⁺ currents in response to depolarization under voltage clamp conditions and are able to generate action potentials. Odontoblasts express neuronal isoforms of 2 and 2 subunits of sodium channels. Co-cultures of odontoblasts with trigeminal neurons indicate a clustering of 2 and 2 sodium channel subunits and, at the sites of cell-cell contact, a co-localization of odontoblasts 2 subunits with peripherin. In vivo, sodium channels are expressed in odontoblasts. Ankyrin_G and 2 co-localize, suggesting a link for signal transduction between axons and odontoblasts. Evidence for excitable properties of odontoblasts and clustering of key molecules at the site of odontoblast-nerve contact strongly suggest that odontoblasts may operate as sensor cells that initiate tooth pain transmission.

Received for publication, February 2, 2006 , and in revised form, June 30, 2006.

^* This work was supported by grants from the French Ministry of Research, Rhone-Alpes region (an emergence grant), INSERM, University Claude Bernard-Lyon I (Centre Technologique des Microstructures and Centre Commun d'Imagerie de Laennec), and European COST Action B23. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ B. Allard and H. Magloire contributed equally to this work.

² To whom correspondence should be addressed: Faculté d'Odontologie, Rue G. Paradin, 69372 Lyon Cedex 08, France. Tel.: 33-4-78-77-86-87; E-mail: magloire{at}sante.univ-lyon1.fr.

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