Mosbacher J, Schoepfer R, Monyer H, Burnashev N, Seeburg P H, Ruppersberg J P
Max-Planck-Institut für medizinische Forschung, Heidelberg, Germany.
Science. 1994 Nov 11;266(5187):1059-62. doi: 10.1126/science.7973663.
The decay of excitatory postsynaptic currents in central neurons mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors is likely to be shaped either by receptor desensitization or by offset after removal of glutamate from the synaptic cleft. Native AMPA receptors show desensitization time constants of 1 to about 10 milliseconds, but the underlying molecular determinants of these large differences are unknown. Cloned AMPA receptors carrying the "flop" splice variants of glutamate receptor subtype C (GluR-C) and GluR-D are shown to have desensitization time constants of around 1 millisecond, whereas those with the "flip" variants are about four times slower. Cerebellar granule cells switch their expression of GluR-D splice variants from mostly flip forms in early stages to predominantly flop forms in the adult rat brain. These findings suggest that rapid desensitization of AMPA receptors can be regulated by the expression and alternative splicing of GluR-D gene transcripts.
由α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体介导的中枢神经元兴奋性突触后电流的衰减，可能是由受体脱敏作用形成的，或者是在从突触间隙去除谷氨酸后形成的偏移造成的。天然AMPA受体的脱敏时间常数为1至约10毫秒，但造成这些巨大差异的潜在分子决定因素尚不清楚。携带谷氨酸受体亚型C（GluR-C）和GluR-D的“翻转”剪接变体的克隆AMPA受体，其脱敏时间常数约为1毫秒，而携带“顺向”变体的受体则慢约四倍。小脑颗粒细胞将其GluR-D剪接变体的表达从早期主要的顺向形式转变为成年大鼠大脑中主要的翻转形式。这些发现表明，AMPA受体的快速脱敏可通过GluR-D基因转录本的表达和可变剪接来调节。
