Antagonism of neuronal kainate receptors by lanthanum and gadolinium
Antagonism of neuronal kainate receptors by lanthanum and gadolinium
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DOI：
10.1016/s0028-3908(98)00082-3
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发表时间：
1998-10-01
影响因子：
4.7
通讯作者：
Wilding, TJ
中科院分区：
文献类型：
--
作者：
Huettner, JE;Stack, E;Wilding, TJ
在培养的大鼠海马神经元、皮层神经元、新分离的背根神经节神经元和表达GluR6海人酸受体亚单位的人胚胎肾293细胞中，研究了镧和Gd对兴奋性氨基酸诱发电流的影响。在所有这些细胞中，由红藻氨酸受体介导的电流都被低浓度的三价离子所拮抗。在负保持电位下，对DRG细胞的抑制IC50值，La为2.8mM，Gd为2.3mM。La可阻断海马神经元和表达GluR6的293细胞的红藻氨酸受体介导的电流，IC50值分别为2.1和4.4mU M。稀土元素的稳态抑制对膜电位的依赖性很小，然而，在阻断开始或恢复的动力学过程中，我们不能解决任何随膜电位的系统变化。抑制不依赖于使用，也不能通过增加激动剂的浓度来克服。这些结果表明，稀土元素可能不会深入离子孔内，也不会直接竞争激动剂的结合部位。与神经性AMPA受体相比，神经性AMPA受体需要100亩以上的稀土元素才能达到半最大阻断，而这些离子对神经元和重组海人藻酸受体的抑制作用明显更强。(C)1998爱思唯尔科学有限公司。保留所有权利。
The effects of lanthanum and gadolinium on currents evoked by excitatory amino acids were studied in cultured rat hippocampal and cortical neurons, in freshly dissociated dorsal root ganglion neurons, and in human embryonic kidney 293 cells expressing the GluR6 kainate receptor subunit. In all of these cells, currents mediated by kainate-preferring receptors were antagonized by low micromolar concentrations of the trivalent ions. At negative holding potentials, the IC50 values for inhibition in DRG cells were 2.8 mu M for La and 2.3 mu M for Gd. Kainate receptor-mediated currents in hippocampal neurons and in 293 cells expressing GluR6 were blocked by La with IC50 values of 2.1 and 4.4 mu M, respectively. Steady-state inhibition by the lanthanides showed very slight dependence on membrane potential, however, we were not able to resolve any systematic variation with membrane potential in the kinetics of block onset or recovery. Inhibition was not use-dependent and was not overcome by increasing the concentration of agonist. These results indicate that lanthanides probably do not bind deep within the ion pore or directly compete for the agonist binding site. In contrast to neuronal AMPA receptors, which require more than 100 mu M lanthanides for half-maximal blockade, the inhibition of neuronal and recombinant kainate receptors by these ions displays significantly higher potency. (C) 1998 Elsevier Science Ltd. All rights reserved.