HCN1 subunits contribute to the kinetics of Ih in neonatal cortical plate neurons
HCN1 subunits contribute to the kinetics of Ih in neonatal cortical plate neurons
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DOI：
10.1002/dneu.22104
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发表时间：
2013-10
影响因子：
3
通讯作者：
L. Stoenica;Wiebke Wilkars;Arne Battefeld;Konstantin Stadler;R. Bender;U. Strauss
中科院分区：
文献类型：
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作者：
L. Stoenica;Wiebke Wilkars;Arne Battefeld;Konstantin Stadler;R. Bender;U. Strauss
神经元中离子通道的分布调节神经元发育过程中的神经元活动和神经元网络的正确形成。其中一个通道是超极化激活环核苷酸门控（HCN）通道，构成超极化激活电流（Ih）的分子底物。我们之前的研究表明，最快激活的亚基 HCN1 在大鼠新生皮质板神经元 Ih 的产生中发挥着作用。为了更好地了解 HCN1 对早期新皮质发育的影响，我们对 HCN1−/− 和对照 HCN1+/+ 小鼠的新生皮质板和幼年第 5 层体感神经元进行了生化分析和全细胞记录。 Western Blot 分析显示，HCN+/+ 小鼠新生皮质板组织中的 HCN1 蛋白表达量仅为年轻成年皮质中 HCN1 的 3%，表明在 HCN1−/− 小鼠中，其他亚型（特别是 HCN4）可能补偿性上调。出生后第一天，HCN1亚基的功能性消融并不影响表达Ih的锥体皮质板神经元的比例。尽管单个亚基蛋白的贡献仍然存在，但 HCN1 的缺乏显着减慢了单个 Ih 表达神经元的电流激活和失活。然而，它并没有损害最大幅度/密度、激活的电压依赖性和 cAMP 敏感性。总之，我们的数据表明，虽然 HCN1 的表达相对较低，但 HCN1 对单个皮质板神经元的 Ih 特性有很大贡献。这些特性在 HCN1−/− 中发生了显着变化，要么是由于 HCN1 本身的缺乏，要么是由于补偿机制。 © 2013 Wiley periodicals, Inc. Develop Neurobiol 73: 785–797, 2013
The distribution of ion channels in neurons regulates neuronal activity and proper formation of neuronal networks during neuronal development. One of the channels is the hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channel constituting the molecular substrate of hyperpolarization‐activated current (Ih). Our previous study implied a role for the fastest activating subunit HCN1 in the generation of Ih in rat neonatal cortical plate neurons. To better understand the impact of HCN1 in early neocortical development, we here performed biochemical analysis and whole‐cell recordings in neonatal cortical plate and juvenile layer 5 somatosensory neurons of HCN1−/− and control HCN1+/+ mice. Western Blot analysis revealed that HCN1 protein expression in neonatal cortical plate tissue of HCN+/+ mice amounted to only 3% of the HCN1 in young adult cortex and suggested that in HCN1−/− mice other isoforms (particularly HCN4) might be compensatory up‐regulated. At the first day after birth, functional ablation of the HCN1 subunit did not affect the proportion of Ih expressing pyramidal cortical plate neurons. Although the contribution of individual subunit proteins remains open, the lack of HCN1 markedly slowed the current activation and deactivation in individual Ih expressing neurons. However, it did not impair maximal amplitude/density, voltage dependence of activation, and cAMP sensitivity. In conclusion, our data imply that, although expression is relatively low, HCN1 contributes substantially to Ih properties in individual cortical plate neurons. These properties are significantly changed in HCN1−/−, either due to the lack of HCN1 itself or due to compensatory mechanisms. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 785–797, 2013