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

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