The Journal of Neurophysiology Vol. 79 No. 1 January 1998, pp. 430-438
Copyright ©1998 The American Physiological Society

NMDA Receptor-Mediated Differential Laminar Susceptibility to the Intracellular Ca²⁺ Accumulation Induced by Oxygen-Glucose Deprivation in Rat Neocortical Slices

Atsuo Fukuda, Kanji Muramatsu, Akihito Okabe, Yasunobu Shimano, Hideki Hida, Ichiro Fujimoto, and Hitoo Nishino

Department of Physiology, Nagoya City University Medical School, Nagoya, Aichi 467, Japan

Fukuda, Atsuo, Kanji Muramatsu, Akihito Okabe, Yasunobu Shimano, Hideki Hida, Ichiro Fujimoto, and Hitoo Nishino. 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 cell. 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 -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 differential [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 in all layers. The laminar difference in terms of the [Ca²⁺]_i increases was abolished by AP5, but not by CNQX. These results indicate that layer 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 IV-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.

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