Mammalian neurons rapidly undergo excitotoxic cell death during anoxia, while neurons from the anoxia-tolerant painted turtle can survive without oxygen for hours without apparent damage. An anoxia-mediated decrease in AMPA receptor currents are an important part of the turtle’s natural defence however the mechanism underlying it is unknown. Here I investigate a mechanism that involves activation of a mitochondrial KATP channel that subsequently signals a decrease in AMPAR currents. Whole-cell AMPAR currents were stable during normoxia, but anoxia or pharmacological activation of mKATP channels resulted in a 50% decrease in AMPAR currents. Conversely, mKATP antagonists blocked the anoxia-mediated decrease. Mitochondrial KCa channel modulators responded similarly. Blocking the Ca2+-uniporter also reduced normoxic AMPAR currents by 40%, and including BAPTA in the recording abolished the anoxia or agonist-mediated decrease. Therefore, the mKATP channel is involved in the anoxia-mediated down-regulation of AMPAR activity and is a common mechanism to reduce glutamatergic excitability.

Mammalian neurons rapidly undergo excitotoxic cell death during anoxia, while neurons from the anoxia-tolerant painted turtle can survive without oxygen for hours without apparent damage. An anoxia-mediated decrease in AMPA receptor currents are an important part of the turtle’s natural defence however the mechanism underlying it is unknown. Here I investigate a mechanism that involves activation of a mitochondrial KATP channel that subsequently signals a decrease in AMPAR currents. Whole-cell AMPAR currents were stable during normoxia, but anoxia or pharmacological activation of mKATP channels resulted in a 50% decrease in AMPAR currents. Conversely, mKATP antagonists blocked the anoxia-mediated decrease. Mitochondrial KCa channel modulators responded similarly. Blocking the Ca2+-uniporter also reduced normoxic AMPAR currents by 40%, and including BAPTA in the recording abolished the anoxia or agonist-mediated decrease. Therefore, the mKATP channel is involved in the anoxia-mediated down-regulation of AMPAR activity and is a common mechanism to reduce glutamatergic excitability.