Referenced in: none

Automatically associated channels: Cav3.2

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

Authors: Fabrice Marger, Agathe Gelot, Abdelkrim Alloui, Julien Matricon, Juan F Sanguesa Ferrer, Christian Barrere, Anne Pizzoccaro, Emilie Muller, Joel Nargeot, Terrance P Snutch, Alain Eschalier, Emmanuel Bourinet, Denis Ardid

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2011 Jul 5 , 108, 11268-73

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21690417

Abstract
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.