Initiation of epileptiform activity by excitatory amino acid receptors in the disinhibited rat neocortex.
1. Intracellular recordings were obtained from neurons in layer II-III of rat frontal cortex maintained in vitro. The role of excitatory amino acid receptors in generation of picrotoxin (PTX)-induced epileptiform activity was investigated with the use of D-2-amino-5-phosphonovaleric acid (D-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) as selective antagonists of N-methyl-D-aspartate (NMDA) and non-NMDA receptors, respectively. 2. Bath application of PTX resulted in a decrease in evoked inhibitory postsynaptic potentials (IPSPs) in neocortical neurons and a concomitant increase in a polysynaptic late excitatory postsynaptic potential (IEPSP). Epileptiform burst responses, termed paroxysmal depolarizing shifts (PDSs), subsequently developed. Based on response duration, two types of PDSs were identified. Long PDSs were greater than 100 ms in duration, whereas short PDSs lasted less than 50 ms. An early depolarizing potential preceded both types of epileptiform burst response. 3. The NMDA receptor antagonist D-APV reduced the peak amplitude and duration of the PDS. D-APV-insensitive portions of the PDS were greatly attenuated or abolished by CNQX. The non-NMDA antagonist also increased the latency to PDS onset and reduced its duration without affecting peak amplitude. CNQX-insensitive components of the PDS, when present, were abolished by D-APV. 4. Short-duration PDSs could be blocked by CNQX. In these neurons, increasing the stimulation strength produced epileptiform responses of reduced amplitude. 5. Under control conditions, PDS amplitude was a linear function of membrane potential, increasing with hyperpolarization and diminishing on depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
W L
WL
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Hablitz
J J
JJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D004560:Electricity; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016202:N-Methylaspartate; D010852:Picrotoxin; D011810:Quinoxalines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate