Kainate, GABAA and NMDA receptors in Xenopus oocytes expressing mRNA from the cortex of mice kindled with FG 7142.
The repeated administration of the beta-carboline, FG 7142, to mice leads to 'chemical kindling', i.e., the development of seizures following doses which were initially insufficient to produce convulsive activity. Messenger RNA (mRNA) was prepared from the cortex of control and FG 7142-treated mice killed at 10-12 days or at 28-45 days after the last kindling injection, and this mRNA was injected into Xenopus oocytes. At 3-4 days following injection, a voltage clamp technique was used to record responses to kainic acid, gamma-aminobutyric acid (GABA), and N-methyl-D-aspartate (NMDA). Kainate was significantly more potent in oocytes expressing mRNA from kindled mice killed at either 10-12 or 28-45 days than in those injected with control mRNA. GABA also was more potent in oocytes with mRNA from kindled mice killed at 10-12 days, but this difference was not present at the longer interval. Chemical kindling did not change the response to NMDA. The current-voltage relation for kainate responses was linear, and plots from kindled and control mRNA were similar. The persistent increase in potency of kainate, an excitatory glutamate ligand, may play a role in producing the lowered FG 7142 threshold characteristic of kindled mice.
Lewin
E
E
Veterans Affairs Medical Center, Denver, CO 80220, USA.
Bleck
V
V
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007608:Kainic Acid / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D007608:Kainic Acid; D016202:N-Methylaspartate; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid