Long-lasting potentiation of epileptiform bursts by group I mGluRs is NMDA receptor independent.
In CA3 pyramidal cells of guinea pig hippocampal slices, picrotoxin (50 microM) elicited spontaneous, rhythmically recurring epileptiform bursts 285-435 ms in duration. The addition of (S)-3, 5-dihydroxyphenylglycine (DHPG, 50 microM, 90 min application), a selective group I metabotropic glutamate receptor (mGluR) agonist, resulted in a rapid-onset transient increase in burst frequency. This was followed by a slowly progressive increase in burst duration, with bursts reaching 1.5-3.8 s in duration at 90 min of DHPG application. The potentiation of epileptiform burst duration persisted at least 2 h after agonist removal. To determine whether N-methyl-D-aspartate (NMDA) receptor activation participates in the mGluR-induced potentiation of epileptiform bursts, experiments were carried out in the presence of D-2-amino-5-phosphonovaleric acid (APV, 50-100 microM), an NMDA receptor antagonist. Application of DHPG in the presence of APV resulted in a significantly enhanced transient increase in burst frequency. Nevertheless, when compared with the control described above, there was no significant alteration in the rate of development of the burst prolongation nor its persistence after washout. In other experiments, application of APV in the presence of fully developed mGluR-induced potentiated bursts (after 90 min washout of DHPG) resulted in no significant change in either burst frequency or duration. The data reveal that both induction and maintenance of group I mGluR-mediated potentiation of epileptiform discharges are NMDA receptor-independent processes, suggesting that epileptogenesis, when induced by group I mGluR activation, may occur and be sustained in the absence of NMDA receptor activation.
Galoyan
S M
SM
Department of Neurology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203, USA.
Merlin
L R
LR
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003292:Convulsants; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000737:chemistry / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D010507:Periodicity; D010852:Picrotoxin; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D008734:Methoxyhydroxyphenylglycol; D010852:Picrotoxin; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C010117:3,4-dihydroxyphenylglycol