Depolarization of mitochondria in isolated CA1 neurons during hypoxia, glucose deprivation and glutamate excitotoxicity

• Published in: Brain research 2006-03, Vol.1077 (1), p.153-160
• Main Authors: Larsen, Geir Arne, Skjellegrind, Håvard K., Berg-Johnsen, Jon, Moe, Morten C., Vinje, Morten Larsen
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; CA1 neuron; Central nervous system; Electrophysiology; Energy Metabolism - physiology; Female; Fundamental and applied biological sciences. Psychology; Glucose - deficiency; Glucose - metabolism; Glutamic Acid - metabolism; Hippocampus; Hippocampus - cytology; Hippocampus - metabolism; Hypoxia; Hypoxia - metabolism; Ischemia; Medical sciences; Membrane Potentials - physiology; Mitochondria; Mitochondria - metabolism; Mitochondrial membrane potential; Mitochondrial Membranes - physiology; Neurology; Neurotoxins - metabolism; Organ Culture Techniques; Rats; Rats, Wistar; Rh 123; Statistics, Nonparametric; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2005.10.095

During cerebral ischemia neuronal injury is induced by a combination of hypoxia, hypoglycemia and glutamate excitotoxicity. To evaluate the relative importance of these factors on the mitochondrial function, acutely isolated rat hippocampal CA1 neurons were loaded with Rhodamine 123 to monitor the mitochondrial membrane potential (Δ ψ m). During 15 min of hypoxia, a rapid and complete mitochondrial depolarization was observed in all neurons also when complex V of the respiratory chain was blocked by oligomycin. Glucose deprivation caused 77% of the neurons to loose the Δ ψ m completely, whereas most oligomycin-treated neurons retained their Δ ψ m. During oxygen and glucose deprivation, a similar mitochondrial response was seen as in hypoxia. Although 15 min of high glutamate concentration (1 mM) provoked a rapid and irreversible increase in [Ca 2+] i, only 25% of the neurons lost the Δ ψ m. All oligomycin-treated neurons, however, lost the Δ ψ m during glutamate exposure. In conclusion, the mitochondrial function of acutely isolated CA1 neurons is more sensitive to hypoxia than to glucose deprivation and glutamate excitotoxicity.