Mammalian neurons are anoxia-sensitive and rapidly undergo excitotoxic cell death when deprived of oxygen, mediated largely by calcium entry through N-methyl-D-aspartate receptors (NMDARs). This does not occur in neurons of the anoxia-tolerant western painted turtle, where a decrease in NMDAR currents is observed with anoxia. This decrease is dependent on a modest increase in cytosolic [Ca2+] during anoxia. The aim of this study was to determine if activation of the mitochondrial permeability transition pore (mPTP) decreases NMDAR currents through release of mitochondrial Ca2+. The data indicate that mPTP opening is sufficient to cause a decrease in NMDAR currents during normoxia and the anoxia-mediated rise in cytosolic [Ca2+] and depolarization of the mitochondrial membrane potential is due to opening of the mPTP. Furthermore, since a mitochondrial uncoupler releases additional calcium during anoxia we speculate that the mitochondrial membrane potential decreases in a regulated fashion to a new set-point.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33238 |
| Date | 20 November 2012 |
| Creators | Hawrysh, Peter |
| Contributors | Buck, Leslie |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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