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Mitochondrial KATP channels attenuate anoxic NMDAR currents via regulation of the mitochondrial Ca2+ uniporter in the western painted turtle
Author(s) -
Pamenter Matthew Edward,
Cooray Mohan,
Buck Leslie Thomas
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a594-b
Subject(s) - uniporter , nmda receptor , mitochondrion , anoxic waters , microbiology and biotechnology , chemistry , biophysics , homeostasis , biology , receptor , biochemistry , cytosol , environmental chemistry , enzyme
Unlike anoxia‐sensitive mammals the western painted turtle survives prolonged periods of anoxia. Likely key is the ability to acutely decrease N‐methyl‐D‐aspartate receptor (NMDAR) activity with the onset of anoxia. Recently, we have shown that mitochondrial K ATP channels (mK ATP ) regulate NMDARs in the anoxic turtle cortex via a Ca 2+ ‐based mechanism. We hypothesized that mK ATP activation in anoxia partially uncouples the mitochondrial membrane potential (Δψ m ), reducing the activity of the Ca 2+ uniporter and thereby altering cellular Ca 2+ homeostasis and subsequently NMDAR activity. NMDAR activity was measured using the whole‐cell patch‐clamp technique and cellular Ca 2+ was measured fluorescently. Mitochondrial uncoupling was measured via the rates of oxygen consumption and ATP synthesis and by changes in (Δψ m . Activation of mK ATP partially uncoupled mitochondria 9–14% and partially depolarized (Δψ m . Ca 2+ fluorescence increased and NMDAR currents decreased with anoxia, mK ATP activation and uniporter blockade. These changes were abolished by activation of the uniporter. mK ATP blockade abolished the anoxic and mK ATP mediated changes but not those mediated by the uniporter. These data show that the anoxic attenuation of the NMDARs is mediated by mitochondrial Ca 2+ handling, which is in turn modulated by mK ATP activity. Supported by an NSERC Grant to LTB.