Stimulation of glutamate receptors in cultured hippocampal neurons causes Ca2+-dependent mitochondrial contraction
| Autor: | Viacheslav Li, Tatiana Brustovetsky, Nickolay Brustovetsky |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Light Physiology Green Fluorescent Proteins NIM811 Glutamic Acid Biology Mitochondrion Mitochondrial apoptosis-induced channel Hippocampus Mitochondrial Membrane Transport Proteins Article Permeability chemistry.chemical_compound Mitochondrial membrane transport protein medicine Animals Molecular Biology Cells Cultured Membrane Potential Mitochondrial Neurons Valinomycin Mitochondrial Permeability Transition Pore Glutamate receptor Depolarization Cell Biology Cell biology Mitochondria Rats medicine.anatomical_structure chemistry Mitochondrial permeability transition pore Receptors Glutamate biology.protein Ruthenium Compounds Calcium Neuron Mitochondrial Swelling |
| Popis: | Cultured hippocampal neurons expressing mitochondrially-targeted enhanced yellow fluorescent protein (mito-eYFP) were used to quantitatively examine mitochondrial remodelling in response to excitotoxic glutamate. Mitochondrial morphology was evaluated using laser spinning-disk confocal microscopy followed by calibrated image processing and 3D image rendering. Glutamate triggered an increase in cytosolic Ca 2+ and mitochondrial depolarization accompanied by Ca 2+ -dependent morphological transformation of neuronal mitochondria from “thread-like” to rounded structures. The quantitative analysis of the mitochondrial remodelling revealed that exposure to glutamate resulted in a decrease in mitochondrial volume and surface area concurrent with an increase in sphericity of the organelles. NIM811, an inhibitor of the mitochondrial permeability transition, attenuated the glutamate-induced sustained increase in cytosolic Ca 2+ and suppressed mitochondrial remodelling in the majority of affected neurons, but it did not rescue mitochondrial membrane potential. Shortening, fragmentation, and formation of circular mitochondria with decreased volume and surface area accompanied mitochondrial depolarization with FCCP. However, FCCP-induced morphological alterations appeared to be distinctly different from mitochondrial remodelling caused by glutamate. Moreover, FCCP prevented glutamate-induced mitochondrial remodelling suggesting an important role of Ca 2+ influx into mitochondria in the morphological alterations. Consistent with this, in saponin-permeabilized neurons, Ca 2+ caused mitochondrial remodelling which could be prevented by Ru 360 . |
| Databáze: | OpenAIRE |
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