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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2011

T-type calcium channels contribute to colonic hypersensitivity in a rat model of irritable bowel syndrome

Fabrice Marger
  • Fonction : Auteur
Agathe Gelot
  • Fonction : Auteur
Abdelkrim Alloui
  • Fonction : Auteur
Julien Matricon
  • Fonction : Auteur
Juan Ferrer
  • Fonction : Auteur
Christian Barrère
  • Fonction : Auteur
Anne Pizzoccaro
  • Fonction : Auteur
Emilie Muller
  • Fonction : Auteur
Joël Nargeot
  • Fonction : Auteur
Terrance Snutch
  • Fonction : Auteur
Alain Eschalier
  • Fonction : Auteur
Emmanuel Bourinet
  • Fonction : Auteur
Denis Ardid
  • Fonction : Auteur

Résumé

The symptoms of irritable bowel syndrome (IBS) include significant abdominal pain and bloating. Current treatments are empirical and often poorly efficacious, and there is a need for the development of new and efficient analgesics aimed at IBS patients. T-type calcium channels have previously been validated as a potential target to treat certain neuropathic pain pathologies. Here we report that T-type calcium channels encoded by the Ca V 3.2 isoform are expressed in colonic nociceptive primary afferent neurons and that they contribute to the exaggerated pain perception in a butyrate-mediated rodent model of IBS. Both the selective genetic inhibition of Ca V 3.2 channels and pharmacological blockade with calcium channel antagonists attenuates IBS-like painful symptoms. Mechanistically, butyrate acts to promote the increased insertion of Ca V 3.2 channels into primary sensory neuron membranes, likely via a posttranslational effect. The butyrate-mediated regulation can be recapitulated with recombinant Ca V 3.2 channels expressed in HEK cells and may provide a convenient in vitro screening system for the identification of T-type channel blockers relevant to visceral pain. These results implicate T-type calcium channels in the pathophysiology of chronic visceral pain and suggest Ca V 3.2 as a promising target for the development of efficient analgesics for the visceral discomfort and pain associated with IBS.

Dates et versions

hal-04320275 , version 1 (04-12-2023)

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Citer

Fabrice Marger, Agathe Gelot, Abdelkrim Alloui, Julien Matricon, Juan Ferrer, et al.. T-type calcium channels contribute to colonic hypersensitivity in a rat model of irritable bowel syndrome. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108 (27), pp.11268-11273. ⟨10.1073/pnas.1100869108⟩. ⟨hal-04320275⟩

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