Involvement of the glutamate transporter and the sodium–calcium exchanger in the hypoxia-induced increase in intracellular Ca 2+ in rat hippocampal slices

Abstract

Hippocampal slices prepared from adult rats were loaded with fura-2 and the intracellular free Ca 2+ concentration ([Ca 2+] i) in the CA1 pyramidal cell layer was measured. Hypoxia (oxygen–glucose deprivation) elicited a gradual increase in [Ca 2+] i in normal Krebs solution. At high extracellular sodium concentrations ([Na +] o), the hypoxia-induced response was attenuated. In contrast, hypoxia in low [Na +] o elicited a significantly enhanced response. This exaggerated response to hypoxia at a low [Na +] o was reversed by pre-incubation of the slice at a low [Na +] o prior to the hypoxic insult. The attenuation of the response to hypoxia by high [Na +] o was no longer observed in the presence of antagonist to glutamate transporter. However, antagonist to Na +–Ca 2+ exchanger only slightly influenced the effects of high [Na +] o. These observations suggest that disturbance of the transmembrane gradient of Na + concentrations is an important factor in hypoxia-induced neuronal damage and corroborates the participation of the glutamate transporter in hypoxia-induced neuronal injury. In addition, the excess release of glutamate during hypoxia is due to a reversal of Na +-dependent glutamate transporter rather than an exocytotic process.