Colonic overexpression of the T-type calcium channel Cav3.2 in a mouse model of visceral hypersensitivity and in irritable bowel syndrome patients

Background Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. Methods This bench-to-bed study combined a preclinical experimental study on mice and a case–control clinical study. Preclinical studies were performed on wild-type and Cav3.2-KO mice. Colonic sensitivity and Cav3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav3.2 expression. Key results Wild-type, but not Cav3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. Conclusions & inferences This translational study supports the involvement of the calcium channels Cav3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.