The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes

Abstract

Glutamate is shown to induce increases in intracellular Ca2+ concentrations ([Ca2+]i), increases in45Ca2+ influx, decreases in the activity of Na+, K+,-ATPase activity, and activation of the Na+/Ca2+ exchanger in rat cerebral cortex synaptosomes. NMDA receptor antagonists virtually prevented these effects. Preincubation of synaptosomes with α-tocopherol, superoxide dismutase, and ganglioside GM1 normalized [Ca2+]i,45Ca2+, influx, and Na+, K+-ATPase activity in rat cerebral cortex synaptosomes exposed to glutamate. Glutamate and GM1 activated the Na+/K+ exchanger, and their effects were additive. Calcium ions entering cerebral cortex nerve cells via NMDA receptors during exposure to high glutamate concentrations appeared to be only the trigger for the processes activating free-radical reactions. Activation of these reactions led to increases in Ca2+ influx into cells, decreases in Na+, K+-ATPase activity, and significant increases in [Ca2+]i, though this could be prevented by antioxidants and gangliosides.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 4, pp. 488–496, April. 1999.

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Avrova, N.F., Shestak, K.I., Zakharova, I.O. et al. The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes. Neurosci Behav Physiol 30, 535–541 (2000). https://doi.org/10.1007/BF02462611

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Key Words

  • Glutamate
  • calcium ions
  • antioxidants
  • GM1 ganglioside
  • brain synaptosomes