Depolarization of mitochondria in isolated CA1 neurons during hypoxia, glucose deprivation and glutamate excitotoxicity.
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 (Deltapsim). 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 Deltapsim completely, whereas most oligomycin-treated neurons retained their Deltapsim. 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 [Ca2+]i, only 25% of the neurons lost the Deltapsim. All oligomycin-treated neurons, however, lost the Deltapsim 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.
University of Oslo, Faculty Division Rikshospitalet, Institute for Surgical Research and Department of Neurosurgery, N-0027 Oslo, Norway. g.a.larsen@labmed.uio.no
Geir Arne
GA
Larsen
Håvard K
HK
Skjellegrind
Jon
J
Berg-Johnsen
Morten C
MC
Moe
Morten Larsen
ML
Vinje
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005947:Glucose / Q000172:deficiency / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000502:physiology; D009498:Neurotoxins / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D009498:Neurotoxins; D018698:Glutamic Acid; D005947:Glucose