CaM kinase II in colonic smooth muscle contributes to dysmotility in murine DSS‐colitis

Background Altered calcium mobilization has been implicated in the development of colonic dysmotility in inflammatory bowel disease. The aim of this study was to investigate the mechanisms by which disrupted intracellular Ca²⁺ signalling contributes to the impaired contractility of colon circular smooth muscles. Methods Acute colitis was induced in C57Bl/6 mice with dextran sulphate sodium (DSS) in the drinking water for 5 days. Key Results Spontaneous and acetylcholine‐evoked contractions, caffeine‐evoked hyperpolarization, and SERCA2 and phospholamban expression were reduced compared with controls. Tetrodotoxin did not restore control levels of contractile activity. The amplitudes, but not the frequency, of intracellular Ca²⁺ waves were increased compared with controls. Caffeine abolished intracellular Ca²⁺ waves in control smooth muscle cells, but not in smooth muscle cells from DSS‐treated mice. CaM kinase II activity and cytosolic levels of HDAC4 were increased, and IκBα levels were decreased in distal colon smooth muscles from DSS‐treated mice. Conclusions & Inferences These results suggest that disruptions in intracellular Ca²⁺ mobilization due to down‐regulation of SERCA2 and phospholamban expression lead to increased CaM kinase II activity and cytosolic HDAC4 that may contribute to the dysmotility of colonic smooth muscles in colitis by enhancing NF‐κB activity.