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

• FELIPE SIMON ; DIEGO VARELA ; ANA RIVEROS ; ANA LUISA EGUIGUREN ; ANDRES STUTZIN ^[1]
  1. [1] Universidad de Chile

     Universidad de Chile

     Santiago, Chile

     
• Localización: Biological Research, ISSN-e 0717-6287, ISSN 0716-9760, Vol. 35, Nº. 2, 2002, págs. 215-222
• Idioma: inglés
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• Resumen

  • 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 (A HREF="#2"Barros et al., 2001a/A). 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