Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons
Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons
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DOI：
10.1523/jneurosci.2667-06.2006
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发表时间：
2006-11-22
影响因子：
5.3
通讯作者：
Johnston, Daniel
中科院分区：
文献类型：
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作者：
Chen, Xixi;Yuan, Li-Lian;Johnston, Daniel
树突反向传播动作电位（bAPs）促进Hebbian长期增强（LTP）的诱导。尽管海马CA1锥体神经元远端树突中的bAPs在从体细胞传播时减弱，但其振幅可以通过下调树突a型K+电流而大大增加。因此，这些电流背后的通道可能代表了导致突触可塑性的信号通路的关键调控成分。我们使用Kv4.2敲除小鼠直接验证了这一假设。Kv4.2基因的缺失和Kv4.2蛋白的缺失导致CA1锥体神经元顶端树突的a型K+电流特异性和几乎完全消除。树突状kv4.2编码的a型K+电流的缺失导致bAP振幅的增加和并发Ca2+内流的增加。此外，Kv4.2敲除小鼠缺乏树突状a型K+电流的CA1锥体神经元在LTP诱导中表现出较低的阈值。另一方面，使用饱和协议触发的LTP在Kv4.2敲除和野生型神经元之间仍然无法区分。我们的研究结果支持了由Kv4.2亚基组成的树突a型K+通道调节动作电位反向传播并诱导特定形式的突触可塑性的假设。
Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increased greatly via downregulation of dendritic A-type K+ currents. The channels that underlie these currents thus may represent a key regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by using Kv4.2 knock-out mice. Deletion of the Kv4.2 gene and a loss of Kv4.2 protein resulted in a specific and near-complete elimination of A-type K+ currents from the apical dendrites of CA1 pyramidal neurons. The absence of dendritic Kv4.2-encoded A-type K+ currents led to an increase of bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ currents from Kv4.2 knock-out mice exhibited a lower threshold than those of wild-type littermates for LTP induction with the use of a theta burst pairing protocol. LTP triggered with the use of a saturating protocol, on the other hand, remained indistinguishable between Kv4.2 knock-out and wild-type neurons. Our results support the hypothesis that dendritic A-type K+ channels, composed of Kv4.2 subunits, regulate action potential backpropagation and the induction of specific forms of synaptic plasticity.