title: Cell volume regulatory ion channels in cell proliferation and cell death.
abstract: Alterations of cell volume are key events during both cell proliferation and apoptotic cell death. Cell proliferation eventually requires an increase of cell volume, and apoptosis is typically paralleled by cell shrinkage. Alterations of cell volume require the participation of ion transport across the cell membrane, including appropriate activity of Cl(-) and K(+) channels. Cl(-) channels modify cytosolic Cl(-) activity and mediate osmolyte flux, and thus influence cell volume. Most Cl(-) channels allow exit of HCO(3)(-), leading to cytosolic acidification, which in turn inhibits cell proliferation and favors apoptosis. K(+) exit through K(+) channels decreases cytosolic K(+) concentration, which may sensitize the cell for apoptotic cell death. K(+) channel activity further maintains the cell membrane potential, a critical determinant of Ca(2+) entry through Ca(2+) channels. Ca(2+) may, in addition, enter through Ca(2+)-permeable cation channels, which, in some cells, are activated by hyperosmotic shock. Increases of cytosolic Ca(2+) activity may trigger both mechanisms required for cell proliferation and mechanisms, leading to apoptosis. Thereby cell proliferation and apoptosis depend on magnitude and temporal organization of Ca(2+) entry, as well as activity of other signaling pathways. Accordingly, the same ion channels may participate in the stimulation of both cell proliferation and apoptosis. Specific ion channel blockers may thus abrogate both cellular mechanisms, depending on cell type and condition.
authors: Department of Physiology, University of Tübingen, Germany.
authors: Florian
authors: F
authors: Lang
authors: Michael
authors: M
authors: Föller
authors: Karl
authors: K
authors: Lang
authors: Philipp
authors: P
authors: Lang
authors: Markus
authors: M
authors: Ritter
authors: Alexey
authors: A
authors: Vereninov
authors: Ildiko
authors: I
authors: Szabo
authors: Stephan M
authors: SM
authors: Huber
authors: Erich
authors: E
authors: Gulbins
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D018118:Chloride Channels / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D050994:Voltage-Dependent Anion Channels / Q000502:physiology
chemical_list: D015220:Calcium Channels; D018118:Chloride Channels; D007473:Ion Channels; D015221:Potassium Channels; D050994:Voltage-Dependent Anion Channels