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Blockade of calcium-permeable AMPA receptors protects hippocampal neurons against global ischemia-induced death
- Source :
- Proceedings of the National Academy of Sciences of the United States. August 23, 2005, Vol. 102 Issue 34, p12230, 6 p.
- Publication Year :
- 2005
-
Abstract
- Transient global or forebrain ischemia induced experimentally in animals can cause selective, delayed neuronal death of hippocampal CA1 pyramidal neurons. A striking feature is a delayed rise in intracellular free [Zn.sup.2+] in CA1 neurons just before the onset of histologically detectable cell death. Here we show that [alpha]-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) at Schaffer collateral to CA1 synapses in postischemic hippocampus exhibit properties of [Ca.sup.2+]/[Zn.sup.2+]-permeable, Glu receptor 2 (GluR2)-lacking AMPARs before the rise in [Zn.sup.2+] and cell death. At 42 h after ischemia, AMPA excitatory postsynaptic currents exhibited pronounced inward rectification and marked sensitivity to 1-naphthyl acetyl spermine (Naspm), a selective channel blocker of GluR2-lacking AMPARs. In control hippocampus, AMPA excitatory postsynaptic currents were electrically linear and relatively insensitive to Naspm. Naspm injected intrahippocampally at 9-40 h after insult greatly reduced the late rise in intracellular free [Zn.sup.2+] in postischemic CA1 neurons and afforded partial protection against ischemia-induced cell death. These results implicate GluR2-lacking AMPA receptors in the ischemia-induced rise in free [Zn.sup.2+] and death of CA1 neurons, although a direct action at the time of the rise in [Zn.sup.2+] is unproven. This receptor subtype appears to be an important therapeutic target for intervention in ischemia-induced neuronal death in humans. glutamate | 1-naphthyl acetyl spermine | neurodegeneration
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 102
- Issue :
- 34
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.136076130