The neuronal channel NALCN contributes resting sodium permeability and is required for normal respiratory rhythm

被引：278

作者：

Lu, Boxun ^{[1
]}

Su, Yanhua ^{[1
]}

Das, Sudipto ^{[1
]}

Liu, Jin ^{[1
]}

Xia, Jingsheng ^{[1
]}

Ren, Dejian ^{[1
]}

机构：

[1] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA

来源：

CELL | 2007年 / 129卷 / 02期

关键词：

D O I：

10.1016/j.cell.2007.02.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：371 / 383

页数：13

共 44 条

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