Functional proteins involved in regulation of intracellular Ca(2+) for drug development: desensitization of N-methyl-D-aspartate receptor channels.
Functional proteins involved in regulation of intracellular Ca(2+) for drug development: desensitization of N-methyl-D-aspartate receptor channels.
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药物开发中参与调节细胞内 Ca(2) 的功能蛋白：N-甲基-D-天冬氨酸受体通道的脱敏。
DOI：
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发表时间：
2005
影响因子：
3.5
通讯作者：
Y. Yoneda
中科院分区：
文献类型：
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作者：
N. Nakamichi;Y. Yoneda
N-甲基-D-天冬氨酸（NMDA）受体是兴奋性配体门控离子通道的主要亚型，在哺乳动物中枢神经系统（CNS）的多种生理和病理过程中起着关键作用。与快速内化的突触非NMDA受体相反，突触NMDA受体已被证明是相当静态的。然而，最近越来越多的证据表明，NMDA受体也可能经历内化。在我们的研究中，重复但不持续的激动剂刺激确实诱导NMDA受体通道的脱敏，这可能是由于细胞表面上表达的NMDA受体的数量减少，以类似于网格蛋白诱导的内吞作用的方式内化。NMDA受体通道的脱敏为阐明突触NMDA受体数量动态调节的基本机制提供了线索，这无疑对维持CNS的完整性和功能性至关重要。
N-Methyl-D-aspartate (NMDA) receptors are a principal subtype of excitatory ligand-gated ion channels with crucial roles in a variety of physiological and pathological processes in the mammalian central nervous system (CNS). In contrast to synaptic non-NMDA receptors that rapidly internalize, synaptic NMDA receptors have been shown to be rather static. However, recent accumulating evidence gives rise to the possibility that NMDA receptors may also undergo internalization. In our studies, repeated but not sustained stimulation by an agonist indeed induced desensitization of NMDA-receptor channels, which may be due to a decrease in the number of NMDA receptors expressed on cellular surfaces by internalization in a manner similar to the clathrin-induced endocytosis. Desensitization of NMDA-receptor channels provides a clue for the elucidation of fundamental mechanisms underlying dynamic regulation of the number of NMDA receptors at synapses, which is undoubtedly critical for the maintenance of both integrity and functionality in the CNS.