NMDA receptor activation accelerates ischemic energy depletion in the hippocampal slice and the demonstration of a threshold for ischemic damage to protein synthesis.
Energy depletion is a primary factor initiating ischemic damage to neurons. In a separate report, we demonstrated that in vitro ischemia inhibits protein synthesis in the CA1 pyramidal neurons of the hippocampal slice via a mechanism involving extracellular calcium and N-methyl-D-aspartate (NMDA) receptor activation during the ischemic episode. In this study, we tested whether these agents accelerated the ischemic energy depletion beyond tolerable levels. ATP and phosphocreatine (PCr) were measured immediately after different durations of in vitro ischemia in the presence or absence of calcium and the NMDA receptor antagonist ketamine. The results support the contention that extracellular calcium does not contribute to the ischemic energy depletion. NMDA receptor activation accelerates the fall in ATP and PCr, but only during the first 45 s of the ischemia. Using protein synthesis inhibition as a functional indicator of ischemic damage in the hippocampal slice, we demonstrated that greater than 2 min of ischemia is necessary to inhibit protein synthesis. Thus, this threshold duration of ischemia indicates that events occurring between 2 and 5 min ischemia result in a prolonged protein synthesis inhibition.
Raley
K M
KM
Department of Physiology, University of Wisconsin-Madison 53706.
Lipton
P
P
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D010725:Phosphocreatine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D010725:Phosphocreatine; D000255:Adenosine Triphosphate