NMDA receptor-mediated differential laminar susceptibility to the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in rat neocortical slices

NMDA receptor-mediated differential laminar susceptibility to the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in rat neocortical slices. J. Neurophysiol. 79: 430-438, 1998. Slices of somatosensory cortex taken from immature rats on postnatal day (P)7-14 were labeled with fura-2. Intracellular Ca2+ concentration ([Ca2+](i)) was monitored in identified pyramidal cells as the ratio of fluorescence intensities (R-F340/F380) during oxygen-glucose deprivation. The R-F340/F380 ([Ca2+](i)) Of individual pyramidal cells was monitored in each of the cortical layers II-VI simultaneously. Neurons in all neocortical layers exhibited significant increases in [Ca2+](i) that varied with the duration of oxygen-glucose deprivation. Individual neurons responded to oxygen-glucose deprivation with abrupt increases in [Ca2+](i) after various latencies. The ceiling level of the [Ca2+](i) increase differed from cell to fell. Neurons in layer II/III showed significantly greater increases in [Ca2+](i) than those in layers IV, V, or VI. Kynurenic acid. a nonselective glutamate receptor antagonist, and bicuculline, a selective gamma-aminobutyric acid (GABA)(A) receptor antagonist, suppressed the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in all neocortical layers examined. After kynurenic acid, but not after bicuculline, there was no longer a different tial [Ca2+](i) increases in layer II/III. Both 2-amino-5-phosphonopentanoic acid (AP5), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, strongly suppressed the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation nail layers. The laminar difference in terms of the [Ca2+](i) increases was abolished by AP5, but not by CNQX. These results indicate that laver II/III cells are the most prone to oxygen-glucose deprivation-induced intracellular Ca2+ accumulation, and that this is primarily mediated by NMDA receptors. Thus, layer II/III neurons would be more likely to suffer cellular Ca2+ overload and excitotoxicity during ischemia than layer TV-VI cells. Such a differential laminar vulnerability might play an important role in determining the pathological characteristics of the immature cortex and its sequelae later in life.