In vitro ischemia and protein synthesis in the rat hippocampal slice: the role of calcium and NMDA receptor activation.
The rat hippocampal slice was developed as a model for investigating the effects of ischemia on protein synthesis in different cell types, as synthesis is an early functional indicator of cell damage. Five min of in vitro ischemia inhibited protein synthesis in CA1 pyramidal and subicular neurons 3 h later, despite recovery of the energy charge. Morphology of these neurons was also affected. In contrast, glia and capillary endothelial cells showed increased synthesis at this time point, and no apparent structural changes. Exposure of slices to buffer lacking calcium and containing the non-competitive NMDA receptor blocker ketamine, during the 5 min ischemia, prevented both the inhibition of protein synthesis and the morphologic changes in the neurons. However, if buffer only lacked calcium, or only contained ketamine, both forms of ischemic damage occurred. Thus, the neuronal protein synthesis inhibition and the impaired morphology appear to be mediated by either extracellular calcium or NMDA receptor activation. In contrast to the neurons, the ischemia-induced stimulation of protein synthesis in glia and capillary endothelial cells was not affected by the above treatments, indicating that neither NMDA receptor activation nor extracellular calcium is necessary for this effect.
Raley-Susman
K M
KM
Department of Physiology, University of Wisconsin-Madison 53706.
Lipton
P
P
D000818:Animals; D002118:Calcium / Q000502:physiology*; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*
D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D002118:Calcium