title: Volume-sensitive outwardly rectifying Cl(-) channels contribute to butyrate-triggered apoptosis of murine colonic epithelial MCE301 cells.
abstract: Butyrate is a fatty acid with an important role in the maintenance of colonic homeostasis. It induces apoptosis in colonic epithelial cells and contributes to the pathogenesis of ulcerative colitis. However, just how how butyrate triggers apoptosis is poorly understood. In our model system of mouse colonic epithelial MCE301 cells, whole-cell patch-clamp recordings revealed the presence of swelling-activated outwardly rectifying chloride ion (Cl(-)) currents. These currents exhibited time-dependent inactivation upon strong depolarization, a low field strength anion selectivity (I(-) > Br(-) > Cl(-) > F(-)), and a sensitivity to 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)oxybutyric acid (DCPIB), a specific blocker of volume-sensitive outwardly rectifying (VSOR) Cl(-) channels. The results of flow cytometric analysis and caspase 3/7 assays demonstrated that exposure of MCE301 cells to sodium butyrate for 16 h triggered apoptotic cell shrinkage, phosphatidylserine exposure, and caspase 3/7 activation. Importantly, the VSOR Cl(-) channel blocker was able to inhibit sodium butyrate-induced apoptotic processes. These results suggest that activation of the VSOR Cl(-) channel is essential for sodium butyrate-triggered apoptosis in MCE301 cells.
authors.affiliation: Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan, takshimi@pha.u-toyama.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hironao
authors.initials: H
authors.lastname: Ohtake
authors.forename: Takuto
authors.initials: T
authors.lastname: Fujii
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D020148:Butyric Acid / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D010718:Phosphatidylserines / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D010718:Phosphatidylserines; D020148:Butyric Acid; D053148:Caspase 3; D053179:Caspase 7