PARTICIPATION OF GABAA-MEDIATED INHIBITION IN ICTAL-LIKE DISCHARGES IN THE RAT ENTORHINAL CORTEX. Valeri Lopantsev and Massimo Avoli. Research Group on Cell Biology of Excitable Tissue, Montreal Neurological Institute, and Departments of Neurology and Neurosurgery, and of Physiology, McGill University, Montreal, QC, Canada, H3A 2B4.
APStracts 4:0250N, 1997.
ABSTRACT
The spontaneous, synchronous activity induced by 4-aminopyridine (4AP;50æM) in the adult rat entorhinal cortex was analyzed with simultaneous field potential and intracellular re~cordings in an in vitro slice preparation. 4AP induced isolated negative-going field potentials (interval of occurrence=27.6ñ9.9s, meansñSD; n=27 slices) that corresponded to intracellular long-lasting depolariza~tions (LLDs), and ictal-like epilep~ti~form discharges (interval of occurrence=10.4ñ5.7min; n=27 slices) that were initiated by the negative field potentials. LLDs recorded with K-acetate-filled microelec~trodes triggered few action potentials of variable amplitude and had a duration of 1.7ñ0.8s (n=26 neurons), a peak amplitude of 11.8ñ5.0mV (n=26 neurons), and a reversal poten~ tial of -66.2 ñ 3.9mV (n=17 neurons). The ictal dis~charges studied with K- acetate microelectrodes consisted of prolonged de~po~lariza~tions (dura~ tion=72.9ñ44.3s; peak amplitude=29.2ñ11.4mV; n=25 neurons) with action potential firing during both the `tonic' and the `clonic' phase; these depolarizations had a reversal potential of -45.3ñ3.8mV (n=4 neurons). Intracellular Cl- diffusion from KCl-filled microelectrodes made both LLDs and ictal depolari~za~tions increase in amplitude (30.5ñ8.2mV; n=8 and 41.8ñ9.8mV; n=6 neurons respectively). LLDs recorded with KCl/QX314 microelec~trodes reached an amplitude of 36.3ñ5.2mV, lasted 12.5ñ6.5s and had a reversal potential of -31.3 ñ2.5mV (n=4 neurons); under these recording procedures the ictal dis~charge amplitude was 41.5ñ5.0mV and the reversal potential - 24.0ñ7.0mV (n=4 neurons). The N-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2-carboxy-piperazine-4-yl)-pro-pyl-l-phosphonate (10æM; n=5 neurons) alone or concomitant with the non-NMDA receptor antagonist 6-cyano-7-nitro- quinoxaline-2,3-dione (10æM; n=4 neurons) abol~ished ictal discharges, without influencing LLDs. LLDs were blocked by the GABAA re~ceptor antagonist bicuculline methiodide (BMI, 10æM; n=6 neurons) or the æ-opioid receptor agonist (D-Ala2-N-Me-Phe,Gly-ol) enkephalin (DAGO, 10æM; n=2 neurons). Application of BMI (n=4 neurons) or DAGO (n=2 neurons) to control the medium, abolished LLDs and ictal discharges, but disclosed a novel type of epileptiform depolarization that lasted 3.5ñ1.2s and occurred every 5.2ñ2.6s (n=6 neurons). Our data indicate that 4AP induces in the rat entorhinal cortex, a synchronous, GABA-mediated potential that is instrumental in initiating NMDA-dependent, ictal discharges. Moreover, we present evidence for an active role played by GABAA-mediated potentials in the maintenance and termination of these prolonged epileptiform events. 

Received 16 December 1996; accepted in final form 9 September 1997.
APS Manuscript Number J983-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997