Requirement of protein synthesis for group I mGluR-mediated induction of epileptiform discharges.
Picrotoxin (50 microM) elicited rhythmic synchronized bursting in CA3 pyramidal cells in guinea pig hippocampal slices. Addition of the selective group I metabotropic glutamate receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (25 microM) elicited an increase in burst frequency. This was soon followed by a slowly progressive increase in burst duration (BD), converting the brief 250-520 ms picrotoxin-induced synchronized bursts into prolonged discharges of 1-5 s in duration. BD was significantly increased within 60 min and reached a maximum after 2-2.5 h of agonist exposure. The protein synthesis inhibitors anisomycin (15 microM) or cycloheximide (25 microM) significantly impeded the mGluR-mediated development of the prolonged bursts; 90-120 min of agonist application failed to elicit the expected burst prolongation. By contrast, the mGluR-mediated enhancement of burst frequency progressed unimpeded. Furthermore, protein synthesis inhibitors had no significant effect on the frequency or duration of fully developed mGluR-induced prolonged discharges. These results suggest that the group I mGluR-mediated prolongation of synchronized bursts has a protein synthesis-dependent mechanism.
Department of Neurology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203, USA.
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology*; D003292:Convulsants; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D010507:Periodicity; D010852:Picrotoxin; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology
D000841:Anisomycin; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D005998:Glycine; D010852:Picrotoxin; D011500:Protein Synthesis Inhibitors; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine