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Simultaneous single neuron recording of O2 consumption, [Ca2+]i and mitochondrial membrane potential in glutamate toxicity.
- Source :
- Journal of Neurochemistry; Apr2009, Vol. 109 Issue 2, p644-655, 12p, 6 Graphs
- Publication Year :
- 2009
-
Abstract
- In order to determine the sequence of cellular processes in glutamate toxicity, we simultaneously recorded O<subscript>2</subscript> consumption, cytosolic Ca<superscript>2+</superscript> concentration ([Ca<superscript>2+</superscript>]<subscript>i</subscript>), and mitochondrial membrane potential (mΔψ) in single cortical neurons. Oxygen consumption was measured using an amperometric self-referencing platinum electrode adjacent to neurons in which [Ca<superscript>2+</superscript>]<subscript>i</subscript> and mΔψ were monitored with Fluo-4 and TMRE<superscript>+</superscript>, respectively, using a spinning disk laser confocal microscope. Excitotoxic doses of glutamate caused an elevation of [Ca<superscript>2+</superscript>]<subscript>i</subscript> followed seconds afterwards by an increase in O<subscript>2</subscript> consumption which reached a maximum level within 1–5 min. A modest increase in mΔψ occurred during this time period, and then, shortly before maximal O<subscript>2</subscript> consumption was reached, the mΔψ, as indicated by TMRE<superscript>+</superscript> fluorescence, dissipated. Maximal O<subscript>2</subscript> consumption lasted up to 5 min and then declined together with mΔψ and ATP levels, while [Ca<superscript>2+</superscript>]<subscript>i</subscript> further increased. mΔψ and [Ca<superscript>2+</superscript>]<subscript>i</subscript> returned to baseline levels when neurons were treated with an NMDA receptor antagonist shortly after the [Ca<superscript>2+</superscript>]<subscript>i</subscript> increased. Our unprecedented spatial and time resolution revealed that this sequence of events is identical in all neurons, albeit with considerable variability in magnitude and kinetics of changes in O<subscript>2</subscript> consumption, [Ca<superscript>2+</superscript>]<subscript>i</subscript>, and mΔψ. The data obtained using this new method are consistent with a model where Ca<superscript>2+</superscript> influx causes ATP depletion, despite maximal mitochondrial respiration, minutes after glutamate receptor activation. [ABSTRACT FROM AUTHOR]
- Subjects :
- GLUTAMIC acid
TOXICITY testing
MITOCHONDRIA
NEURONS
NERVOUS system
Subjects
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 109
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 36982973
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2009.05997.x