ROLE OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES IN THE PATTERNING OF
EPILEPTIFORM ACTIVITIES IN VITRO.
Lisa R. Merlin, Gregory W. Taylor, and Robert K.S. Wong.
Departments of Neurology and Pharmacology, State University of New York
Health Science Center, Brooklyn, New York 11203-2098.
APStracts 2:0151N, 1995.
SUMMARY AND CONCLUSIONS
(1) Epileptiform activities were elicited from the in vitro guinea pig
hippocampus by the addition of picrotoxin. Modification of the picrotoxin-
induced activities by agents active at metabotropic glutamate receptors
(mGluRs) was examined using intracellular and extracellular recordings. (2)
Picrotoxin typically elicited synchronized discharges (epileptiform bursts) in
CA3 neurons. These spontaneously occurred at regular intervals. In the
presence of (+)-[alpha]-methyl-4-carboxyphenylglycine (MCPG; 700-1000 [mu]M),
an antagonist at multiple mGluR subtypes, the frequency of spontaneous
epileptiform bursts decreased. In contrast, when the mGluR agonists (1S,3R)-1-
aminocyclopentane- 1,3-dicarboxylic acid (ACPD; 5 [mu]M) or (2S,3S,4S)-
[alpha]-(carboxycyclopropyl)- glycine (L-CCG-I; 10 [mu]M) were added to the
incubating medium, the frequency of epileptiform bursts increased. No
consistent change in membrane potential, burst duration, nor burst
afterhyperpolarization was associated with the changes in burst frequency. (3)
When spontaneous burst frequency was reduced in MCPG, stimulation at a higher
frequency entrained bursts without failure. Bursts evoked in MCPG were similar
in waveform and amplitude to those evoked in the control state. (4) (S)-4-
carboxyphenylglycine (S-4CPG) and (R,S)-4-carboxy-3-hydroxyphenylglycine (RS-
4C3HPG) are antagonists at mGluR subtypes 1 and 5 but agonists at mGluRs 2 and
3. Addition of either of these agents increased the frequency of epileptiform
bursts. (5) These results suggest that sufficient glutamate is released during
epileptiform activities to activate mGluRs. The overall effect is to increase
the frequency of synchronized discharges. This modulatory action on burst
frequency is probably mediated via the mGluR 2 and 3 receptor subclass.
Received 22 March 1995; accepted in final form 5 May 1995.
APS Manuscript Number J193-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 May 1995.