Postischemic enhancements of N-methyl-D-aspartic acid (NMDA) and non-NMDA receptor-mediated responses in hippocampal CA1 pyramidal neurons.
Glutamate receptor-mediated responses were investigated by using a whole-cell recording and an intracellular calcium ion ([Ca2+]i) imaging in gerbil postischemic hippocampal slices prepared at 1, 3, 6, 9, 12, and 24 hours after 5-minute ischemia. Bath application of N-methyl-D-aspartic acid (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate showed that NMDA-, AMPA- and kainate-induced currents were enhanced in postischemic CA1 pyramidal neurons at 1 to 12 hours after 5-minute ischemia. NMDA and non-NMDA receptor-mediated excitatory postsynaptic currents (EPSC) were examined in postischemic CA1 pyramidal neurons at 3 hours after 5-minute ischemia to confirm whether synaptic responses are enhanced in the postischemic CA1 pyramidal neurons. The amplitudes of NMDA- and non-NMDA-receptor-mediated EPSC were enhanced in the postischemic CA1 pyramidal neurons. NMDA-, AMPA-, and kainate-induced [Ca2+]i elevations were also examined to determine whether the enhancement of currents is accompanied by the enhancement of [Ca2+]i elevation. The enhancements of NMDA-, AMPA-, and kainate-induced [Ca2+]i elevations were shown in the postischemic CA1. These results indicate that NMDA and non-NMDA receptor-mediated responses are persistently enhanced in the CA1 pyramidal neurons 1 to 12 hours after transient ischemia, and suggest that the enhancement of glutamate receptor-mediated responses may act as one of crucial factors in the pathologic mechanism responsible for leading postischemic CA1 pyramidal neurons to irreversible neuronal injury.
Mitani
A
A
Department of Physiology, School of Medicine, Ehime University, Japan.
Namba
S
S
Ikemune
K
K
Yanase
H
H
Arai
T
T
Kataoka
K
K
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D004553:Electric Conductivity; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D017966:Pyramidal Cells / Q000502:physiology*; D017459:Receptors, Amino Acid / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015424:Reperfusion
D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium