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

Felipe Simon, Diego Varela, Ana Riveros, Ana Luisa Eguiguren, Andres Stutzin

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)215-222
Number of pages8
JournalBiological Research
Issue number2
Publication statusPublished - 2002


  • Cell death
  • Cell volume
  • Flufenamic acid
  • Nonselective cation channels

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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