Axon terminal hyperexcitability associated with epileptogenesis in vitro. II. Pharmacological regulation by NMDA and GABAA receptors.
1. The preceding report presented evidence that the kindling-like induction of electrographic seizures (EGSs) in the hippocampal slice is accompanied by a lasting increase in the excitability of CA3 axon terminals, which is manifested by an increase in action-potential initiation at this site. In this report we explore the role of the N-methyl-D-aspartate (NMDA) receptor in the induction and maintenance of this antidromic firing, as well as the role of the gamma-aminobutyric acid type A (GABAA) receptor in regulating this activity once it has been induced. 2. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed in control artificial cerebrospinal fluid (ACSF), the frequency of axon terminal firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE P << 0.01). The prior application of the competitive NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV, 50 or 100 microM) prevented the induction of EGSs and suppressed the increase in terminal firing seen in control ACSF (mean increase 1.06 +/- 1.11 spikes/min, P < 0.02). However, when D-APV was applied only after EGSs and antidromic spikes were induced in control ACSF, it failed to alter the frequency of terminal firing (mean 6.44 +/- 2.03 in control ACSF, 8.89 +/- 2.31 in APV; P >> 0.1). Thus the NMDA receptor is required for the induction but not maintenance of increased axon terminal firing, as we previously have shown to be the case for EGSs.(ABSTRACT TRUNCATED AT 250 WORDS)
Stasheff
S F
SF
Department of Pharmacology, Duke University Medical Center, Durham 27710.
Mott
D D
DD
Wilson
W A
WA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001418:Baclofen / Q000494:pharmacology; D046508:Culture Techniques; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; D010852:Picrotoxin; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate