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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 of America; 8/23/2005, Vol. 102 Issue 34, p12230-12235, 6p
- 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<superscript>2+</superscript> in CA1 neurons just before the onset of histologically detectable cell death. Here we show that a-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) at Schaffer collateral to CA1 synapses in postischemic hippocampus exhibit properties of Ca<superscript>2+</superscript>/Zn<superscript>2+</superscript>-permeable, Glu receptor 2 (GluR2)-lacking AMPARs before the rise in Zn<superscript>2+</superscript> 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<superscript>2+</superscript> 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<superscript>2+</superscript> and death of CA1 neurons, although a direct action at the time of the rise in Zn<superscript>2+</superscript> is unproven. This receptor subtype appears to be an important therapeutic target for intervention in ischemia-induced neuronal death in humans. [ABSTRACT FROM AUTHOR]
- Subjects :
- HIPPOCAMPUS (Brain)
CEREBRAL cortex
ISCHEMIA
NERVOUS system
CELL death
SYNAPSES
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 102
- Issue :
- 34
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 18209854
- Full Text :
- https://doi.org/10.1073/pnas.0505408102