DPP6 establishes the A-type K(+) current gradient critical for the regulation of dendritic excitability in CA1 hippocampal neurons.
DPP6 establishes the A-type K(+) current gradient critical for the regulation of dendritic excitability in CA1 hippocampal neurons.
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DOI：
10.1016/j.neuron.2011.08.008
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发表时间：
2011-09-22
期刊：
影响因子：
16.2
通讯作者：
Hoffman DA
中科院分区：
文献类型：
--
作者：
Sun W;Maffie JK;Lin L;Petralia RS;Rudy B;Hoffman DA
亚阈值激活的a型K+电流对大脑的正常功能至关重要，它们起到延迟兴奋和调节放电频率的作用。在CA1海马锥体神经元树突中，a型K+电流密度随着离体细胞距离的增加而增加，在突触整合和可塑性中起重要作用。然而，这种梯度背后的机制仍然难以捉摸。在这里，缺乏Kv4跨膜辅助亚基DPP6的小鼠的树突记录显示，该蛋白对产生a电流梯度至关重要。DPP6的缺失导致a型电流的减少，特别是在远端树突。电流密度的降低伴随着通道激活的电压依赖性的去极化移位。这些变化共同导致树突过度兴奋，树突AP反向繁殖增强，钙电生成和突触长期增强的诱导。尽管树突兴奋性增强，但在DPP6-KO记录中，体电流注射引起的放电行为主要不受影响，表明神经元兴奋性的区隔调节。
Subthreshold-activating A-type K+ currents are essential for the proper functioning of the brain where they act to delay excitation and regulate firing frequency. In CA1 hippocampal pyramidal neuron dendrites, the density of A-type K+ current increases with distance from the soma, playing an important role in synaptic integration and plasticity. The mechanism underlying this gradient has, however, remained elusive. Here, dendritic recordings from mice lacking the Kv4 transmembrane auxiliary subunit DPP6 revealed that this protein is critical for generating the A-current gradient. Loss of DPP6 led to a decrease in A-type current, specifically in distal dendrites. Decreased current density was accompanied by a depolarizing shift in the voltage-dependence of channel activation. Together these changes resulted in hyperexcitable dendrites with enhanced dendritic AP back-propagation, calcium electrogenesis and induction of synaptic long-term potentiation. Despite enhanced dendritic excitability, firing behavior evoked by somatic current injection was mainly unaffected in DPP6-KO recordings, indicating compartmentalized regulation of neuronal excitability.
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