Oxidative stress affects the selective ion permeability of voltage-sensitive Ca2+ channels in cultured retinal cells

Neurosci Res. 1997 Apr;27(4):323-34. doi: 10.1016/s0168-0102(96)01165-0.


The effect of ascorbate/Fe2+-induced oxidative stress on the intracellular Ca2+ concentration ([Ca2+]i) and on the voltage-sensitive Ca2+ channels (VSCC) of chick retinal cells was evaluated in this study. We also analyzed the effect of oxidation on the intracellular Na+ concentration ([Na+]i) and on the Ca2+-dependent release of [3H])gamma-aminobutric acid (GABA) evoked by 50 mM KCI. The resting [Ca2+]i was not affected by oxidation, but the [Ca2+]i response (delta[Ca2+]i) to K+-depolarization was significantly inhibited under oxidative stress conditions. The Ca2+ influx stimulated by membrane depolarization was mediated by L- and N-type VSCC, and by N-metyl-D-aspartate (NMDA) receptor channel, activated by endogenous glutamate released by glutamatergic cells. In cultured retinal cells L-type channels are the major route of Ca2+ influx during depolarization and the most affected by oxidative stress. The N-type VSCC seem not to be affected by oxidant conditions; they were found to be involved in glutamatergic transmission and only indirectly in the release of [3H]GABA evoked by K+-depolarization. Although the Ca2+-dependent release of [3H]GABA evoked by 50 mM KCl is mediated by Ca2+ entry through L-type Ca2+ channels, it is not affected by pre-incubation with the oxidant pair. The oxidative stress conditions increased the [Na+]i in Ca2+-free medium, by a process dependent of Na+ entry through L-type VSCC. The increased permeability of L-type VSCC to Na+ may increase the Ca2+-independent release of endogenous glutamate which, by activating the NMDA receptors, induces the release of [3H]GABA by reversal of its transporter. The equilibrium between the release of GABA and glutamate may play an in important role in neuroprotection against excitotoxic insults.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Chick Embryo
  • Electrophysiology
  • Excitatory Amino Acid Agents / pharmacology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • Neurotransmitter Agents / metabolism
  • Oxidative Stress / drug effects*
  • Permeability
  • Potassium Chloride / pharmacology
  • Retina / cytology
  • Retina / drug effects
  • Retina / metabolism*
  • gamma-Aminobutyric Acid / metabolism


  • Antioxidants
  • Calcium Channel Blockers
  • Calcium Channels
  • Excitatory Amino Acid Agents
  • Neurotransmitter Agents
  • gamma-Aminobutyric Acid
  • Potassium Chloride
  • Ascorbic Acid