Tong G, Shepherd D, Jahr C E
Vollum Institute, Oregon Health Sciences University, Portland 97201-3098.
Science. 1995 Mar 10;267(5203):1510-2. doi: 10.1126/science.7878472.
Desensitization is a phenomenon that is common to many ligand-gated ion channels but has been demonstrated only rarely with physiological stimulation. Numerous studies describe desensitization of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor by exogenous agonists, but whether synaptic stimulation causes desensitization has been unknown. Synaptic stimulation of NMDA receptors on rat hippocampal neurons resulted in desensitization that was prevented by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), adenosine-5'-O-(3-thiotriphosphate) (ATP-gamma-S), or inhibitors of phosphatase 2B (calcineurin), but not by inhibitors of phosphatases 1 and 2A or of tyrosine phosphatases. Synaptic NMDA receptors may fluctuate between phosphorylated and dephosphorylated forms, depending on the rate of synaptic stimulation and the magnitude of the associated influx of calcium through NMDA receptors.
脱敏是许多配体门控离子通道共有的一种现象，但仅在生理刺激下很少被证实。大量研究描述了谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型被外源性激动剂脱敏的情况，但突触刺激是否会导致脱敏尚不清楚。对大鼠海马神经元上的NMDA受体进行突触刺激会导致脱敏，而细胞内的1,2-双（邻氨基苯氧基）乙烷-N,N,N',N'-四乙酸（BAPTA）、腺苷-5'-O-（3-硫代三磷酸）（ATP-γ-S）或磷酸酶2B（钙调神经磷酸酶）抑制剂可阻止这种脱敏，而磷酸酶1和2A或酪氨酸磷酸酶抑制剂则不能。突触NMDA受体可能会在磷酸化和去磷酸化形式之间波动，这取决于突触刺激的速率以及通过NMDA受体的相关钙内流的大小。
