Functional Proteins Involved in Regulation of Intracellular Ca2+ for Drug Development: Desensitization of N-Methyl-D-aspartate Receptor Channels

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  • Nakamichi Noritaka
    Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology
  • Yoneda Yukio
    Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology

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  • Desensitization of N-Methyl-D-aspartate Receptor Channels

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N-Methyl-<sc>D</sc>-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.<br>

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