Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons
Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons
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DOI：
10.1016/j.neuron.2007.05.026
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发表时间：
2007-06-21
期刊：
影响因子：
16.2
通讯作者：
Hoffman, Dax A.
中科院分区：
文献类型：
--
作者：
Kim, Jinhyun;Jung, Sung-Cheri;Hoffman, Dax A.
电压门控性A型K+通道Kv4.2亚单位在海马CA1区神经元的树突中高度表达。然而，很少有人知道的亚细胞分布和贩运Kv4.2含有通道。在这里，我们提供的证据，活动依赖性贩运Kv4.2在海马棘和树突。实时成像和电生理记录表明，谷氨酸受体刺激后，Kv4.2内化被迅速诱导。Kv4.2的内化是网格蛋白介导的，需要NMDA受体激活和Ca2+内流。在分离的海马神经元中，mEPSC振幅依赖于功能性Kv4.2表达水平，并通过诱导Kv4.2内化的刺激而增强。短暂的甘氨酸应用诱导的长时程增强（LTP）导致含GluR 1的AMPA受体沿着Kv 4.2内化在突触插入。我们还发现了证据Kv4.2内化后，突触诱发的LTP在海马脑片培养的CA1神经元。这些结果通过Kv4.2通道表面表达的活性依赖性调节为突触整合和可塑性提供了额外的机制。
Voltage-gated A-type K+ channel Kv4.2 sub-units are highly expressed in the dendrites of hippocampal CA1 neurons. However, little is known about the subcellular distribution and trafficking of Kv4.2-containing channels. Here we provide evidence for activity-dependent trafficking of Kv4.2 in hippocampal spines and dendrites. Live imaging and electrophysiological recordings showed that Kv4.2 internalization is induced rapidly upon glutamate receptor stimulation. Kv4.2 internalization was clathrin mediated and required NMDA receptor activation and Ca2+ influx. In dissociated hippocampal neurons, mEPSC amplitude depended on functional Kv4.2 expression level and was enhanced by stimuli that induced Kv4.2 internalization. Long-term potentiation (LTP) induced by brief glycine application resulted in synaptic insertion of GluR1-containing AMPA receptors along with Kv4.2 internalization. We also found evidence of Kv4.2 internalization upon synaptically evoked LTP in CA1 neurons of hippocampal slice cultures. These results present an additional mechanism for synaptic integration and plasticity through the activity-dependent regulation of Kv4.2 channel surface expression.