Heterogeneity of the calcium-induced permeability transition in isolated non-synaptic brain mitochondria

Kristián, Tibor and Weatherby, Tina M. and Bates, Timothy E. and Fiskum, Gary (2002) Heterogeneity of the calcium-induced permeability transition in isolated non-synaptic brain mitochondria. Journal of Neurochemistry, 83 (6). pp. 1297-308. ISSN 0022-3042

Full content URL: http://dx.doi.org/10.1046/j.1471-4159.2002.01238.x

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Item Type:Article
Item Status:Live Archive

Abstract

Calcium overload of neural cell mitochondria plays a key role in excitotoxic and ischemic brain injury. This study tested the hypothesis that brain mitochondria consist of subpopulations with differential sensitivity to calcium-induced inner membrane permeability transition, and that this sensitivity is greatly reduced by physiological levels of adenine nucleotides. Isolated non-synaptosomal rat brain mitochondria were incubated in a potassium-based medium in the absence or presence of ATP or ADP. Measurements were made of medium and intramitochondrial free calcium, light scattering, mitochondrial ultrastructure, and the elemental composition of electron-opaque deposits within mitochondria treated with calcium. In the absence of adenine nucleotides, calcium induced a partial decrease in light scattering, accompanied by three distinct ultrastructural morphologies, including large-amplitude swelling, matrix vacuolization and a normal appearance. In the presence of ATP or ADP the mitochondrial calcium uptake capacity was greatly enhanced and calcium induced an increase rather than a decrease in mitochondrial light scattering. Approximately 10% of the mitochondria appeared damaged and the rest contained electron-dense precipitates that contained calcium, as determined by electron-energy loss spectroscopy. These results indicate that brain mitochondria are heterogeneous in their response to calcium. In the absence of adenine nucleotides, approximately 20% of the mitochondrial population exhibit morphological alterations consistent with activation of the permeability transition, but less than 10% exhibit evidence of osmotic swelling and membrane disruption in the presence of ATP or ADP.

Additional Information:First published online December 11 2002
Keywords:brain, mitochondria, calcium, permeability transition pore
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B131 Cellular Pathology
B Subjects allied to Medicine > B140 Neuroscience
B Subjects allied to Medicine > B132 Pathobiology
Divisions:College of Science > School of Life Sciences
ID Code:5254
Deposited On:08 Jun 2013 08:09

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