Role of glutamate and GABA transporters in development of pentylenetetrazol-kindling.
Kindling is a form of epileptogenesis that can be induced with pentylenetetrazol (PTZ). We undertook this study to evaluate the contribution of glutamate and GABA transporters to the process of PTZ kindling. Rats were injected i.p. three times per week with PTZ (40 mg/kg) until they were fully kindled. In rats who achieved full kindling, measurement of hippocampal glutamate and GABA transporters within 24 h by western blot showed that GLAST, GLT-1, and EAAC1 were elevated significantly. However, fully kindled rats at 30 days after their last seizure had no change in either glutamate or GABA transporters proteins. These sequential observations suggest that glutamate transporters may contribute to the occurrence of seizures, but were not associated with maintenance of epileptogenesis. During this experiment, we collected data from animals that had kindled easily and animals who were resistant to kindling. Easily-kindled rats reached full kindling with less than five injections of PTZ. Kindling resistant animals failed to achieve full kindling even after administration of 12 consecutive injections of PTZ. Levels of EAAC1 and GAT-1 in easily-kindled rats were decreased by 30% when compared to kindling resistant animals at 30 days after the last PTZ injection. Since decreased EAAC1 and GAT-1 would diminish GABA function, less quantity of these proteins would appear to be associated with the convulsive threshold at the beginning of kindling development. We wonder if glutamate and GABA transporters might be operant in a convulsion threshold set factor or as a pace factor for kindling.
Doi
Taku
T
Section of Psychiatry, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan. takud@med.miyazaki-u.ac.jp
Ueda
Yuto
Y
Nagatomo
Keiko
K
Willmore
L James
LJ
D000818:Animals; D015153:Blotting, Western; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D007696:Kindling, Neurologic / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050485:GABA Plasma Membrane Transport Proteins; C493398:Slc1a1 protein, rat; C493392:Slc1a3 protein, rat; C493415:Slc6a1 protein, rat; D018698:Glutamic Acid; D010433:Pentylenetetrazole