Regulation of extracellular glutamate levels in the long-term anoxic turtle striatum: coordinated activity of glutamate transporters, adenosine, K (ATP) (+) channels and GABA.
Early in anoxia the mammalian brain experiences an uncontrolled release of glutamate, which combined with the failure of glutamate reuptake mechanisms, leads to massive neurotoxic increases in extracellular glutamate. By contrast, the anoxia tolerant turtle (Trachemys scripta) shows no increase in extracellular glutamate levels over many hours of anoxia. During the first hours of anoxia extracellular glutamate levels are maintained by a reduction in glutamate release (mainly due to the inhibition of neuronal vesicular glutamate release), combined with continued uptake by still active glutamate transporters. The early down-regulation in glutamate release is modulated by adenosine receptors and K (ATP) (+) channels, but is not affected by GABA(A )receptors. During long-term anoxia there is a further reduction in the rate of glutamate release, reaching 30% of normoxic control values at 5 h of anoxia. Adenosine and GABA(A) receptors but not K (ATP) (+) channels regulate this reduction in glutamate release. We conclude that the reduction in glutamate release during progressive anoxia is a dynamic process requiring continuous but changing synergistic activity of K (ATP) (+) channels, adenosine and GABA(A) receptors. The fact that there is a still active glutamate release and uptake in prolonged anoxia suggests that extracellular glutamate has a vital function in the deeply hypometabolic brain.
Thompson
John W
JW
Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA. jthompson@med.miami.edu
Prentice
Howard M
HM
Lutz
Peter L
PL
D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D054086:KATP Channels / Q000378:metabolism*; D008954:Models, Biological; D017072:Neostriatum / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014426:Turtles; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
D054086:KATP Channels; D011963:Receptors, GABA-A; D018047:Receptors, Purinergic P1; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid