The Journal of Neurophysiology Vol. 79 No. 1 January 1998, pp. 352-360
Copyright ©1998 The American Physiological Society

Participation of GABA_A-Mediated Inhibition in Ictallike Discharges in the Rat Entorhinal Cortex

Valeri Lopantsev and Massimo Avoli

Research Group on Cell Biology of Excitable Tissue, Montreal Neurological Institute; and Department of Neurology and Neurosurgery and Department of Physiology, McGill University, Montreal, Quebec H3A 2B4, Canada

Lopantsev, Valeri and Massimo Avoli. Participation of GABA_A-mediated inhibition in ictallike discharges in the rat entorhinal cortex. J. Neurophysiol. 79: 352-360, 1998. The spontaneous, synchronous activity induced by 4-aminopyridine (4AP, 50 µM) in the adult rat entorhinal cortex was analyzed with simultaneous field potential and intracellular recordings in an in vitro slice preparation. Four-AP induced isolated negative-going field potentials (interval of occurrence = 27.6 ± 9.9 (SD) s; n = 27 slices) that corresponded to intracellular long-lasting depolarizations (LLDs), and ictallike epileptiform discharges (interval of occurrence = 10.4 ± 5.7 min; n = 27 slices) that were initiated by the negative field potentials. LLDs recorded with K-acetate-filled microelectrodes triggered few action potentials of variable amplitude and had a duration of 1.7 ± 0.8 s (n = 26 neurons), a peak amplitude of 11.8 ± 5.0 mV (n = 26 neurons) and a reversal potential of 66.2 ± 3.9 mV (n = 17 neurons). The ictal discharges studied with K-acetate microelectrodes consisted of prolonged depolarizations (duration = 72.9 ± 44.3 s; peak amplitude = 29.2 ± 11.4 mV; n = 25 neurons) with action-potential firing during both the tonic and the clonic phase. These depolarizations had a reversal potential of 45.3 ± 3.8 mV (n = 4 neurons). Intracellular Cl diffusion from KCl-filled microelectrodes made both LLDs and ictal depolarizations increase in amplitude (30.5 ± 8.2 mV, n = 8 and 41.8 ± 9.8 mV, n = 6 neurons, respectively). LLDs recorded with KCl and 2-(trimethyl-amino)N-(2,6-dimethylphenyl)-acetamide (QX-314) microelectrodesreached an amplitude of 36.3 ± 5.2 mV, lasted 12.5 ± 6.5 s, and had a reversal potential of 31.3 ± 2.5 mV (n = 4 neurons); under these recording procedures the ictal discharge amplitude was 41.5 ± 5.0 mV and the reversal potential 24.0 ± 7.0 mV (n = 4 neurons). The N-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2-carboxy-piperazine-4-yl)-pro-pyl-l-phosphonate (10 µM, n = 5 neurons) alone or concomitant with the nonNMDA receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (10 µM, n = 4 neurons) abolished ictal discharges, without influencing LLDs. LLDs were blocked by the -aminobutyric acid-A (GABA_A) receptor antagonist bicuculline methiodide (BMI, 10 µM, n = 6 neurons) or the µ-opioid receptor agonist (D-Ala2-N-Me-Phe, Gly-ol) enkephalin (DAGO, 10 µM, 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 3.5 ± 1.2 s and occurred every 5.2 ± 2.6 s (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 GABA_A-mediated potentials in the maintenance and termination of these prolonged epileptiform events.

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