title: Human odontoblasts express functional thermo-sensitive TRP channels: implications for dentin sensitivity.
abstract: Odontoblasts form the outermost cellular layer of the dental pulp where they have been proposed to act as sensory receptor cells. Despite this suggestion, evidence supporting their direct role in mediating thermo-sensation and nociception is lacking. Transient receptor potential (TRP) ion channels directly mediate nociceptive functions, but their functional expression in human odontoblasts has yet to be elucidated. In the present study, we have examined the molecular and functional expression of thermo-sensitive TRP channels in cultured odontoblast-like cells and in native human odontoblasts obtained from healthy wisdom teeth. PCR and western blotting confirmed gene and protein expression of TRPV1, TRPA1 and TRPM8 channels. Immunohistochemistry revealed that these channels were localised to odontoblast-like cells as determined by double staining with dentin sialoprotein (DSP) antibody. In functional assays, agonists of TRPV1, TRPA1 and TRPM8 channels elicited [Ca2+]i transients that could be blocked by relevant antagonists. Application of hot and cold stimuli to the cells also evoked rises in [Ca2+]i which could be blocked by TRP-channel antagonists. Using a gene silencing approached we further confirmed a role for TRPA1 in mediating noxious cold responses in odontoblasts. We conclude that human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth. Cultured and native human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth.
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK Laboratoire IMEB, Faculté d Odontologie, Université de la Méditerranée, Marseille, France.
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: El Karim
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Linden
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Curtis
authors.forename: Imad
authors.initials: I
authors.lastname: About
authors.forename: Mary K
authors.initials: MK
authors.lastname: McGahon
authors.forename: Chris R
authors.initials: CR
authors.lastname: Irwin
authors.forename: Fionnuala T
authors.initials: FT
authors.lastname: Lundy
mesh_terms: D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D003080:Cold Temperature / Q000009:adverse effects; D003807:Dentin Sensitivity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism / Q000473:pathology; D009804:Odontoblasts / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050916:TRPV Cation Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013697:Thermosensing / Q000235:genetics; D050051:Transient Receptor Potential Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels