Bowie Derek, Lange G David
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Neurosci. 2002 May 1;22(9):3392-403. doi: 10.1523/JNEUROSCI.22-09-03392.2002.
Potassium (K+) channels and ionotropic glutamate receptors (iGluRs) fulfill divergent roles in vertebrate nervous systems. Despite this, however, recent work suggests that these ion channels are structurally homologous, sharing an ancestral protein, architectural design, and tetrameric subunit stoichiometry. Their gating mechanisms also are speculated to have overlapping features. Here we show that the mechanism of iGluR desensitization is unique. Unlike K+ channels, AMPA- and kainate-type iGluR subunits desensitize in several ordered conformational steps. AMPA receptors operate as dimers, whereas the functional stoichiometry of kainate receptor desensitization is dependent on external ions. Contrary to conventional understanding, kinetic models suggest that partially desensitized AMPA and kainate receptors conduct ions and are likely participants in synaptic signaling. Although sharing many structural correlates with K+ channels, iGluRs have evolved unique subunit-subunit interactions, tailoring their gating behavior to fulfill distinct roles in neuronal signaling.
钾离子(K⁺)通道和离子型谷氨酸受体(iGluRs)在脊椎动物神经系统中发挥着不同的作用。然而,尽管如此,最近的研究表明,这些离子通道在结构上具有同源性,共享一个祖先蛋白、结构设计和四聚体亚基化学计量。它们的门控机制也被推测具有重叠的特征。在这里,我们表明iGluR脱敏的机制是独特的。与K⁺通道不同,AMPA型和海人藻酸型iGluR亚基在几个有序的构象步骤中发生脱敏。AMPA受体以二聚体形式发挥作用,而海人藻酸受体脱敏的功能化学计量取决于外部离子。与传统认识相反,动力学模型表明,部分脱敏的AMPA和海人藻酸受体能够传导离子,并且可能参与突触信号传递。尽管iGluRs与K⁺通道有许多结构上的关联,但它们已经进化出独特的亚基-亚基相互作用,调整其门控行为以在神经元信号传递中发挥不同的作用。