Cofilin is essential for actin filament remodeling in various cell types. We previously reported that ouabain leads to dephosphorylation of cofilin, resulting in cytoskeletal reorganization and cell volume change. We report here that the extracellular [K+](e) deprivation causes dephosphorylation of cofilin with disruption of cytoskeletal structures and cell shrinkage. These changes can be reversed by time-dependent restoration of [K+](c). Thus, these results suggest that the acute shift of [K+](e) triggers a reversible change of cofilin phosphorylation which may be an essential event in the regulation of cytoskeletal architecture and cell volume. (c) 2006 Elsevier Inc. All rights reserved.