The neuronal channel NALCN contributes resting sodium permeability and is required for normal respiratory rhythm
The neuronal channel NALCN contributes resting sodium permeability and is required for normal respiratory rhythm
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DOI：
10.1016/j.cell.2007.02.041
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发表时间：
2007-04-20
期刊：
影响因子：
64.5
通讯作者：
Ren, Dejian
中科院分区：
文献类型：
--
作者：
Lu, Boxun;Su, Yanhua;Ren, Dejian
钠在决定神经系统基础兴奋性方面起着关键作用，它通过静息的Na+渗漏来决定神经系统的基础兴奋性，但TTX和Cs+抗性的Na+渗漏电导的分子特性完全未知。在这里，我们证明了这种电导是由蛋白NALCN形成的，NALCN是钠/钙通道家族中一个基本上没有特征的成员。与其他20个家族成员不同，NALCN形成一个电压无关、非选择性的阳离子通道。NALCN突变小鼠呼吸节律严重紊乱，出生后24小时内死亡。脑干-脊髓记录。显示神经元放电减少。突变的海马神经元中不存在抗TTX和Cs+的背景Na+泄漏电流。突变神经元的静息膜电位对胞外Na+浓度的变化相对不敏感。因此，NALCN，一个非选择性的阳离子通道，形成背景Na+泄漏电导，控制神经元的兴奋性。
Sodium plays a key role in determining the basal excitability of the nervous systems through the resting '' leak '' Na+ permeabilities, but the molecular identities of the TTX- and Cs+-resistant Na+ leak conductance are totally unknown. Here we show that this conductance is formed by the protein NALCN, a substantially uncharacterized member of the sodium/calcium channel family. Unlike any of the other 20 family members, NALCN forms a voltage-independent, nonselective cation channel. NALCN mutant mice have a severely disrupted respiratory rhythm and die within 24 hours of birth. Brain stem-spinal cord recordings. reveal reduced neuronal firing. The TTX- and Cs+-resistant background Na+ leak current is absent in the mutant hippocampal neurons. The resting membrane potentials of the mutant neurons are relatively insensitive to changes in extracellular Na+ concentration. Thus, NALCN, a nonselective cation channel, forms the background Na+ leak conductance and controls neuronal excitability.