Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 33, Issue 10, Pages 1582-1594Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2013.113
Keywords
glutamate release; presynaptic NMDA receptors; spreading depression
Categories
Funding
- Canadian Institutes of Health Research [MOP-8545, MOP-11512, TCE-117869]
- Taiwan National Science Council [NSC 100-2632-B-039-001-MY3, NSC101-2314-B-039-001]
- CMUH [DMR-101-121]
- Taiwan Department of Health Clinical Trial and Research Center of Excellence [DOH102-TD-B-111-004]
Ask authors/readers for more resources
Spreading depression (SD) is a slowly propagating neuronal depolarization that underlies certain neurologic conditions. The wavelike pattern of its propagation suggests that SD arises from an unusual form of neuronal communication. We used enzyme-based glutamate electrodes to show that during SD induced by transiently raising extracellular K+ concentrations ([K+](o)) in rat brain slices, there was a rapid increase in the extracellular glutamate concentration that required vesicular exocytosis but unlike fast synaptic transmission, still occurred when voltage-gated sodium and calcium channels (VGSC and VGCC) were blocked. Instead, presynaptic N-methyl-D-aspartate (NMDA) receptors (NMDARs) were activated during SD and could generate substantial glutamate release to support regenerative glutamate release and propagating waves when VGSCs and VGCCs were blocked. In calcium-free solutions, high [K+](o) still triggered SD-like waves and glutamate efflux. Under such a condition, glutamate release was blocked by mitochondrial Na+/Ca2+ exchanger inhibitors that likely blocked calcium release from mitochondria secondary to NMDA-induced Na+ influx. Therefore presynaptic NMDA receptor activation is sufficient for triggering vesicular glutamate release during SD via both calcium entry and release from mitochondria by mitochondrial Na+/Ca2+ exchanger. Our observations suggest that presynaptic NMDARs contribute to a cycle of glutamate-induced glutamate release that mediate high [K+](o)-triggered SD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available