Glutamate-mediated extrasynaptic inhibition:: Direct coupling of NMDA receptors to Ca2+-activated K+ channels
Glutamate-mediated extrasynaptic inhibition:: Direct coupling of NMDA receptors to Ca2+-activated K+ channels
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DOI：
10.1016/s0896-6273(01)00428-7
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发表时间：
2001-09-27
期刊：
影响因子：
16.2
通讯作者：
Murphy, GJ
中科院分区：
文献类型：
--
作者：
Isaacson, JS;Murphy, GJ
NMDA受体(NMDAR)在中枢神经系统兴奋性突触传递中起重要作用。虽然通过NMDAR的钙离子内流在突触可塑性中起着关键作用，但NMDAR介导的钙内流对神经元兴奋性的直接作用尚不清楚。在这里，我们证明了通过NMDAR的钙内流与大鼠嗅球颗粒细胞外膜贴片上BK型钙激活K+通道的激活直接耦合。重复刺激嗅球切片中的谷氨酸能突触，在颗粒细胞中引起一种缓慢的抑制性突触后电流(IPSC)，这需要NMDAR和BK通道。谷氨酸摄取阻滞剂增强了缓慢的IPSO，提示突触外NMDAR是该反应的基础。这些发现揭示了突触外NMDAR在大脑中的一种新的抑制作用。
NMDA receptors (NMDARs) typically contribute to excitatory synaptic transmission in the CNS. While Ca2+ influx through NMDARs plays a critical role in synaptic plasticity, direct actions of NMDAR-mediated Ca2+ influx on neuronal excitability have not been well established. Here we show that Ca2+ influx through NMDARs is directly coupled to activation of BK-type Ca2+-activated K+ channels in outside-out membrane patches from rat olfactory bulb granule cells. Repetitive stimulation of glutamatergic synapses in olfactory bulb slices evokes a slow inhibitory postsynaptic current (IPSC) in granule cells that requires both NMDARs and BK channels. The slow IPSO is enhanced by glutamate uptake blockers, suggesting that extrasynaptic NMDARs underlie the response. These findings reveal a novel inhibitory action of extrasynaptic NMDARs in the brain.