Journal article
Altered distribution of mitochondria impairs calcium homeostasis in rat hippocampal neurons in culture
Journal of neurochemistry, v 87(1), pp 85-94
Oct 2003
PMID: 12969255
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The specificity of Ca2+ signals is conferred in part by limiting changes in cytosolic Ca2+ to subcellular domains. Mitochondria play a major role in regulating Ca2+ in neurons and may participate in its spatial localization. We examined the effects of changes in the distribution of mitochondria on NMDA-induced Ca2+ increases. Hippocampal cultures were treated with the microtubule-destabilizing agent vinblastine, which caused the mitochondria to aggregate and migrate towards one side of the neuron. This treatment did not appear to decrease the energy status of mitochondria, as indicated by a normal membrane potential and pH gradient across the inner membrane. Moreover, electron microscopy showed that vinblastine treatment altered the distribution but not the ultrastructure of mitochondria. NMDA (200 micro m, 1 min) evoked a greater increase in cytosolic Ca2+ in vinblastine-treated cells than in untreated cells. This increase did not result from impaired Ca2+ efflux, enhanced Ca2+ influx, opening of the mitochondrial permeability transition pore or altered function of endoplasmic reticulum Ca2+ stores. Ca2+ uptake into mitochondria was reduced by 53% in vinblastine-treated cells, as reported by mitochondrially targeted aequorin. Thus, the distribution of mitochondria maintained by microtubules is critical for buffering Ca2+ influx. A subset of mitochondria close to a Ca2+ source may preferentially regulate Ca2+ microdomains, set the threshold for Ca2+-induced toxicity and participate in local ATP production.
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Details
- Title
- Altered distribution of mitochondria impairs calcium homeostasis in rat hippocampal neurons in culture
- Creators
- Guang Jian Wang - University of Minnesota Medical CenterJoshua G JacksonStanley A Thayer
- Publication Details
- Journal of neurochemistry, v 87(1), pp 85-94
- Grant note
- DA11806 / NIDA NIH HHS DA07304 / NIDA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000185316600010
- Scopus ID
- 2-s2.0-0141755101
- Other Identifier
- 991021900192204721
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences