VOLTAGE-DEPENDENT BLOCK BY MG-2+ OF NMDA RESPONSES IN SPINAL-CORD NEURONS

VOLTAGE-DEPENDENT BLOCK BY MG-2+ OF NMDA RESPONSES IN SPINAL-CORD NEURONS
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DOI:
10.1038/309261a0
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发表时间:
1984-01-01
期刊:
影响因子:
64.8
通讯作者:
GUTHRIE, PB
GUTHRIE, PB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
MAYER, ML;WESTBROOK, GL;GUTHRIE, PB

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酸性氨基酸是假定的兴奋性突触transmitters 1,2,离子机制,这是不是很清楚。最近对选择性激动剂和拮抗剂的研究表明,哺乳动物中枢神经系统的神经元具有几种不同的酸性氨基酸受体3,4,这些受体又与单独的传导机制偶联5。N-甲基-D-天冬氨酸(NMDA)是这些受体之一的选择性激动剂3,4。作用于NMDA受体的氨基酸的兴奋作用对膜电位非常敏感,并且已经表明NMDA受体与电压敏感性电导偶联6 -9。最近,膜片钳实验表明,通过L-谷氨酸激活的离子通道的电流通过Mg 2+的电压依赖性阻断10。现在,我们使用电压钳实验小鼠脊髓神经元,NMDA作用的电压敏感性大大降低,从细胞外液中撤出生理浓度(约1 mM)的Mg 2+。这进一步证明了Mg 2+阻断了通过与NMDA受体连接的离子通道的内向电流。
Acidic amino acids are putative excitatory synaptic transmitters1,2, the ionic mechanism of which is not well understood. Recent studies with selective agonists and antagonists suggest that neurones of the mammalian central nervous system possess several different receptors for acidic amino acids3,4, which in turn are coupled to separate conductance mechanisms5.N-methyl-D-aspartic acid (NMDA) is a selective agonist for one of these receptors3,4. The excitatory action of amino acids acting at NMDA receptors is remarkably sensitive to the membrane potential and it has been suggested that the NMDA receptor is coupled to a voltage-sensitive conductance6–9. Recently, patch-clamp experiments have shown the voltage-dependent block by Mg2+of current flow through ion channels activated byL-glutamate10. We now show using voltage-clamp experiments on mouse spinal cord neurones that the voltage-sensitivity of NMDA action is greatly reduced on the withdrawal of physiological concentrations (∼1 mM) of Mg2+from the extracellular fluid. This provides further evidence that Mg2+blocks inward current flow through ion channels linked to NMDA receptors.