Glutamate transport in rat cerebellar granule cells is impaired by inorganic epileptogenic agents.
There is evidence that extracellular glutamate levels are elevated in certain brain regions immediately prior to and during induction and propagation of seizures. There appears to be a correlation between the capacity of removing released glutamate and the genesis of epileptiform activity. Some models make use of metals, such as Co(2+) and Ni(2+), to induce epilepsy. We used patch-clamp recordings to measure the electrogenic glutamate transport in neuronal cells. The present results indicate that Co(2+) (1 mM) and Ni(2+) (5 mM) blocked glutamate transport by 17.6+/-3.9% (n=5, P<0.05) and by 31.8+/-6.2% (n=7, P<0.05), respectively. Ni(2+) inhibited glutamate uptake in a dose-dependent manner. The IC(50) value obtained was 66.6 microM and the maximum inhibition was 40%. We conclude that one mechanism that may explain the seizures induced by exposure to those divalent cations is inhibition of the glutamate transporter.
Mafra
R A
RA
Departamento de Fisiologia, CCBI, Universidade Federal de Alagoas, Maceió-AL, Brazil.
Araújo
D A
DA
Beirão
P S
PS
Cruz
J S
JS
D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003035:Cobalt / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D027322:Amino Acid Transport System X-AG; D003292:Convulsants; D003035:Cobalt; D018698:Glutamic Acid; D009532:Nickel