Voltage-gated Sodium Channels Confer Excitability to Human Odontoblasts

Abstract

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.

L’odontoblaste

“…En effet, un grand nombre de ces canaux ont été identifiés dans la membrane des odontoblastes : canaux Na + dépendant du voltage, canaux K + , canaux Cl -, et canaux Ca 2+ [16][17][18]. Plus particulière-ment, les canaux mécanosensibles K Ca (canaux K + activés par le Ca 2+ ), activés par l'étirement membranaire et concentrés au pôle apical, pourraient jouer un rôle dans la transduction des évènements sensoriels touchant l'organe dentaire.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…The main function of odontoblasts is to deposit a mineralized Ca 2+ matrix, which, in turn, is converted into dentin during tooth development and repair. Whereas it is generally accepted that odontoblasts may double as cellular sensors [in support of this hypothesis, they express both voltage-gated Na + channels (Allard et al, 2006) and store-operated Ca 2+ channels (Shibukawa and Suzuki, 2003)], the expression of thermoTRP channels in odontoblasts (and their role in toothache, the so-called odontoblast transducer theory of dental pain; Fig. 24B) remains controversial.…”

TRP Channels in Dental Pain

“…Odontoblasts are cells that deposit a calcium matrix to form dentin during tooth development and throughout the lifetime for dentin repair. However, because odontoblasts constitute the outermost cell layer of the dental pulp where temperature of oral cavity is first transmitted, the sensory role of odontoblasts is proposed by several lines of independent studies [17][18][19][20][21].…”

“…The strategic location of odontoblasts prompted the investigation that odontoblasts might play a sensory role as well. Evidence supporting that odontoblasts are excitable cells include expression of voltage-gated Na + channels [18], voltage-gated K + channels [33], calciumactivated K + channels [21], store-operated calcium channels [34], Na + /Ca 2+ exchanger [35] and TREK-1 channels [19].…”