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Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation
Author(s) -
Alano Conrad C.,
Beutner Gisela,
Dirksen Robert T.,
Gross Robert A.,
Sheu SheyShing
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.0022-3042.2001.00738.x
Subject(s) - nmda receptor , mitochondrial permeability transition pore , mitochondrion , microbiology and biotechnology , programmed cell death , biophysics , biology , glutamate receptor , intracellular , calcium , homeostasis , chemistry , receptor , biochemistry , apoptosis , organic chemistry
Deregulation of the intracellular Ca 2+ homeostasis by NMDA receptor activation leads to neuronal cell death. Induction of the mitochondrial permeability transition pore (MPT) by Ca 2+ is a critical event in mediating cell death. In this study, we used fluorescent Ca 2+ indicators to investigate the effect of high concentrations of NMDA on cytosolic and mitochondrial Ca 2+ concentrations ([Ca 2+ ] c and [Ca 2+ ] m , respectively) in cultured striatal neurons. Exposure to NMDA resulted in an immediate, sustained increase in [Ca 2+ ] c followed by a secondary increase in [Ca 2+ ] c . This second increase of [Ca 2+ ] c was prevented by pretreatment with N ‐methyl‐valine‐4‐cyclosporin (NMV‐Cys). Exposure of neurons to NMDA also resulted in an increase in [Ca 2+ ] m that was followed by a precipitous decrease in the rhod‐2 signal. This decrease followed the time frame of the secondary increase in [Ca 2+ ] c . Preincubation of the neurons with NMV‐Cys prevented the decrease in rhod‐2 fluorescence. These dynamic changes in the rhod‐2 signal and [Ca 2+ ] m in response to NMDA were confirmed by using confocal microscopy. The presented results indicate that MPT can be detected in living neurons using fluorescent Ca 2+ indicators, which would allow the study of the physiological role of MPT in cell death.