一种改变N-甲基-D-天冬氨酸受体通道镁离子阻滞作用的突变。
A mutation that alters magnesium block of N-methyl-D-aspartate receptor channels.
作者信息
Sharma G, Stevens C F
机构信息
Neuroscience Department, University of California at San Diego, La Jolla 92093, USA.
出版信息
Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9259-63. doi: 10.1073/pnas.93.17.9259.
Abstract
N-Methyl-D-aspartate (NMDA) receptors are blocked at hyperpolarizing potentials by extracellular Mg ions. Here we present a detailed kinetic analysis of the Mg block in recombinant wild-type and mutant NMDA receptors. We find that the Mg binding site is the same in the wild-type and native hippocampal NMDA receptor channels. In the mutant channels, however, Mg ions bind with a 10-fold lower affinity. On the basis of these results, we propose that the energy well at the Mg binding site in the mutants is shallow and the binding is unstable because of an increase in the rate of dissociation. We postulate that the dipole formed by the amide group of asparagine 614 of the epsilon 1 subunit contributes to the structure of the binding site but predict that additional ligands will be involved in coordinating Mg ions.
摘要
N-甲基-D-天冬氨酸（NMDA）受体在超极化电位下会被细胞外镁离子阻断。在此，我们对重组野生型和突变型NMDA受体中的镁离子阻断进行了详细的动力学分析。我们发现野生型和天然海马体NMDA受体通道中的镁离子结合位点相同。然而，在突变型通道中，镁离子的结合亲和力降低了10倍。基于这些结果，我们提出突变体中镁离子结合位点的能量阱较浅，且由于解离速率增加，结合不稳定。我们推测由ε1亚基的天冬酰胺614的酰胺基团形成的偶极有助于结合位点的结构，但预测还会有其他配体参与镁离子的配位。
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