Involvement of the glutamate transporter and the sodium-calcium exchanger in the hypoxia-induced increase in intracellular Ca2+ in rat hippocampal slices.
Hippocampal slices prepared from adult rats were loaded with fura-2 and the intracellular free Ca2+ concentration ([Ca2+]i) in the CA1 pyramidal cell layer was measured. Hypoxia (oxygen-glucose deprivation) elicited a gradual increase in [Ca2+]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+-Ca2+ 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.
Yamaguchi
S
S
Department of Physiology, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Tochigi 321-0293, Japan.
Endo
K
K
Kitajima
T
T
Ogata
H
H
Hori
Y
Y
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D015764:Bepridil / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents; D003998:Dicarboxylic Acids / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016257:Fura-2; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009924:Organ Culture Techniques; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D003998:Dicarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D019831:Sodium-Calcium Exchanger; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015764:Bepridil; D015763:2-Amino-5-phosphonovalerate; C083486:pyrrolidine-2,4-dicarboxylic acid; D012964:Sodium; D002118:Calcium; D016257:Fura-2