LacKamp A, Zhang G-C, Mao L-M, Fibuch E E, Wang J Q
Department of Anesthesiology, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.
Br J Anaesth. 2009 Apr;102(4):515-22. doi: 10.1093/bja/aep009. Epub 2009 Feb 17.
Anaesthetics may target ionotropic glutamate receptors in brain cells to produce their biological actions. Membrane-bound ionotropic glutamate receptors undergo dynamic trafficking between the surface membrane and intracellular organelles. Their subcellular distribution is subject to modulation by changing synaptic inputs and determines the efficacy and strength of excitatory synapses. It has not been explored whether anaesthesia has any impact on surface glutamate receptor expression. In this study, the effect of general anaesthesia on expression of N-methyl-D-aspartate (NMDA) receptors in the surface and intracellular pools of cortical neurones was investigated in vivo.
General anaesthesia was induced by intraperitoneal injection of chloral hydrate in adult male mice. Surface protein cross-linking assays were performed to detect changes in distribution of NMDA receptor subunits (NR1, NR2A, and NR2B) in the surface and intracellular compartments of cerebral cortical neurones.
Chloral hydrate did not alter the total amounts of NR1, NR2A, and NR2B proteins in cortical neurones. However, the drug reduced NR1 proteins in the surface pool of these neurones, and induced a proportional increase in NR1 in the intracellular pool. Similar redistribution of NR2B subunits was observed between the two distinct pools. The changes in NR1 and NR2B were rapid and remained throughout the duration of anaesthesia. NR2A proteins were not altered in the surface or intracellular pool in response to chloral hydrate.
These data demonstrate that subcellular expression of NR1 and NR2B in cortical neurones is sensitive to anaesthesia. Chloral hydrate reduces surface-expressed NMDA receptors (specifically NR2B-containing NMDA receptors) in these neurones in vivo.
麻醉剂可能作用于脑细胞中的离子型谷氨酸受体以发挥其生物学作用。膜结合离子型谷氨酸受体在细胞膜表面和细胞内细胞器之间进行动态转运。它们的亚细胞分布会因突触输入的变化而受到调节，并决定兴奋性突触的效能和强度。麻醉是否会对表面谷氨酸受体表达产生影响尚未得到研究。在本研究中，在体内研究了全身麻醉对皮质神经元表面和细胞内池N-甲基-D-天冬氨酸（NMDA）受体表达的影响。
通过腹腔注射水合氯醛诱导成年雄性小鼠全身麻醉。进行表面蛋白交联分析以检测NMDA受体亚基（NR1、NR2A和NR2B）在大脑皮质神经元表面和细胞内区室中的分布变化。
水合氯醛未改变皮质神经元中NR1、NR2A和NR2B蛋白的总量。然而，该药物减少了这些神经元表面池中的NR1蛋白，并导致细胞内池中NR1成比例增加。在两个不同池之间观察到NR2B亚基的类似重新分布。NR1和NR2B的变化迅速，并在麻醉持续期间一直存在。水合氯醛处理后，NR2A蛋白在表面或细胞内池中未发生改变。
这些数据表明皮质神经元中NR1和NR2B的亚细胞表达对麻醉敏感。水合氯醛在体内减少了这些神经元表面表达的NMDA受体（特别是含NR2B的NMDA受体）。
