Physiological and molecular mechanisms contribute to altered smooth muscle contractility during dextran sodium sulfate-induced colitis in mice

Gastrointestinal tract inflammation evokes alteration of intestinal smooth muscle contractility. The aims of this study were to determine whether colonic smooth muscle responds abnormally during acute inflammation and if these alterations are correlated with changes of myosin isoform composition. Inflammation was induced in female C57BL/6 mice by the addition of 2.5% dextran sodium sulphate (DSS) to the drinking water for 7 days. Mouse circular colonic smooth muscle strips from normal and DSS-inflamed mice were prepared to evaluate contractile responses. Whereas non-receptor stimulation was diminished (1.7-fold), carbachol-induced contraction was enhanced (4.3-fold) in DSS-treated mice during acute inflammation. Ca2+-sensitization of contractile elements induced by carbachol was not different between DSS-treated and control mice. In addition, the Ca2+ sensitivity was decreased for Ca2+ concentrations lower than 320 nM and increased for concentrations higher than 355 nM. Real-time PCR experiments showed a slight increase for all the myosin isoforms in DSS-inflamed mice. The greatest change of expression was found for the LC17b myosin isoform (3.5-fold). Western blot analysis showed no differences in the protein expression for all the myosin isoforms. These data suggest that abnormal colonic contractility is not related to changes in myosin isoform content, but may be associated with alterations in the Ca2+ sensitivity of the contractile elements.