Responses to N-methyl-D-aspartate are enhanced in rats with petit mal-like seizures.

The responses to the glutamate agonist N-methyl-D-aspartate (NMDA) were studied in the sensori-motor cortex of rats with petit mal-like seizures. In a first study, the changes in extracellular concentration of calcium elicited through ionophoretic application of NMDA at various depths in the cortex were measured in vivo. The results show that in the cortex of epileptic rats the NMDA responses are much more widely distributed than in the cortex of control rats. In a second study, a current-source density analysis of the responses elicited through electrical stimulation of the white matter was performed in slices of neocortex in vitro. These findings show that the NMDA-dependent component of the synaptic responses are more widely distributed and of longer duration in the cortex of epileptic rats than in that of control rats. Taken together, these results suggest that in this model of absence epilepsy NMDA-dependent mechanisms are important in the triggering and maintenance of epileptic activity.

Ionic changes induced by excitatory amino acids in the rat cerebral cortex.

The ionic mechanisms underlying the action of excitatory amino acids were investigated in the rat motor cortex. Ion-selective microelectrodes were attached to micropipettes such that their tips were very close and local changes in extracellular concentration of sodium, calcium, and potassium ions elicited through ionophoretic applications of glutamate (Glu) and of its agonists N-methyl-D-aspartate (NMDA), quisqualate (Quis), and kainate (Ka) were measured. These agents produced moderate increases in [K+]o (up to 13 mM) but, in contrast, substantial tetrodotoxin-insensitive decreases in [Na+]o (maximally of 60 mM). NMDA-induced sodium responses could be blocked by manganese, while the Quis- and Ka-induced responses were not. Quis and Ka produced increases in [Ca2+]o or biphasic responses while NMDA, even with small doses, induced each time drastic decreases in [Ca2+]o (maximally of 1.15 mM), which could be attenuated or blocked by manganese but not by organic calcium channel blockers. NMDA responses could be abolished by reduced doses of 2-amino-phosphonovalerate. The largest Glu- and NMDA-induced calcium responses were observed in the superficial cortical layers, but such maxima disappeared after selective degeneration of pyramidal tract neurons. All amino acids produced sizeable reductions in the extracellular space volume. The following can be concluded. (i) All the excitatory amino acids tested induce an increased permeability to sodium and potassium ions. (ii) In addition, the NMDA-operated channels have specifically a large permeability for calcium, although calcium ions contribute only by less than 10% to the NMDA-induced inward currents.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term alterations in amino acid-induced ionic conductances in chronic epilepsy.

Extracellular free sodium (Na+)o and calcium (Ca2+)o concentration changes were measured in the rat motor cortex, using ion-selective microelectrodes. During ionophoretic applications of excitatory amino acids, decreases in (Na2+)o and in (Ca2+)o were observed. Ca2+ signals were not or very little modified by applications of tetrodotoxin while Na+ signals were slightly depressed, up to 20%. Laminar profile analysis revealed that, while the magnitude of Na+ signals was rather constant throughout the cortex, Ca2+ signals were largest in upper cortical layers. Lesioning and pharmacological experiments indicated that the corresponding permeabilities were most probably located on apical dendrites of pyramidal tract neurons. The relative amplitude of Na+ and Ca2+ signals induced by the release of the glutamate agonists N-methyl-D-aspartate, quisqualate and kainate and the shape of the laminar profile of such responses indicated that different ionic permeabilities located on different neurons underlie such responses. Similar experiments performed on chronic epileptogenic motor foci in rats indicated that the amino acid-induced ionic responses were altered. The significance of such alterations for epileptogenesis is discussed.