- 作者: John W. Thompson; Howard M. Prentice; Peter L. Lutz
- 作者服務機構: 1 Department of Biological Sciences, Florida Atlantic University, Boca Raton, Fl, 33431, USA; ; 2 Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, P.O. Box 0161189 (R-189) Miami, Fl, 33101, USA; ; 3 Department of Biomedical Sciences, Florida Atlantic University, Boca Raton, Fl, 33431, USA
- 中文摘要: --
- 英文摘要: 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 GABAa 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 GABAA 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 GABAA 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.
- 中文關鍵字: --
- 英文關鍵字: preconditioning, glutamate, adenosine, anoxia, GABA, K+ATP channels, turtle, ischemia