Decrease in activity of smooth muscle L-type Ca 2ϩ channels and its reversal by NF-B inhibitors in Crohn's colitis model. Am J Physiol Gastrointest Liver Physiol 285: G483-G493, 2003. First published March 19, 2003 10.1152/ajpgi.00038.2003.-We investigated the mechanisms of dysmotility of the colonic circular muscle of the Crohn's disease rat model. Contractions induced by KCl, carbachol, and Bay K 8644 were decreased in circular smooth muscles isolated from 2,4,6-trinitrobenzenesulfonic acid

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... NBS)-induced colitis rat colon. However, the absolute force and Ca 2ϩ sensitivity of contractile proteins were not affected as assessed in ␣-toxin permeabilized smooth muscle. The current density of the L-type Ca 2ϩ channel in circular smooth muscle cells was significantly decreased in the TNBS-treated colonic cells. However, expressions of the L-type Ca 2ϩ channel mRNA and protein did not differ between control and TNBS-treated preparations. Pretreatment with the NF-B inhibitors pyrrolidinedithiocarbamate and sulfasalazine partially recovered the decreased contractility and current density of the L-type Ca 2ϩ channel by TNBS treatment. These results suggest that the decrease in the contraction of circular smooth muscle isolated from TNBS-induced colitis rat colon, which may be related to gut dysmotility in Crohn's disease, is attributable to the decreased activity of the L-type Ca 2ϩ channel. The dysfunction of the L-type Ca 2ϩ channel may be mediated by NF-Bdependent pathways.