Non-selective cation channels and oxidative stress- induced cell swelling

necrosis is considered as a non-specific form of cell death that induces tissue inflammation and is preceded by cell swelling. this increase in cell volume has been ascribed mainly to defective outward pumping of na+ caused by metabolic depletion and/or to increased na+ influx via membrane transporters. a specific mechanism of swelling and necrosis driven by the influx of na+ through nonselective cation channels has been recently proposed (barros et al., 2001a). we have characterized further the properties of the nonselective cation channel (nscc) in htc cells. the nscc shows a conductance of ~18 ps, is equally permeable to na+ and k+, impermeant to ca2+, requires high intracellular ca2+ as well as low intracellular atp for activation and is inhibited by flufenamic acid. hydrogen peroxide induced a significant increase in cell volume that was dependent on external na+. we propose that the nscc, which is ubiquitous though largely inactive in healthy cells, becomes activated under severe oxidative stress. the ensuing na+ influx initiates via positive feedback a series of metabolic and electrolytic disturbances, resulting in cell death by necrosis