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Cited by 381Ion channel regulation and functionNeuroscience of respiration and sleepIon Transport and Channel Regulation

The Neuronal Channel NALCN Contributes Resting Sodium Permeability and Is Required for Normal Respiratory Rhythm

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Lu, Boxun, Su, Yanhua, Das, Sudipto, Liu, Jin, Xia, Jingsheng, Ren, Dejian·2007·Cell
DOI 10.1016/j.cell.2007.02.041
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Abstract

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.

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  • The NALCN neuronal Na+ channel, which like CnCch1 lacks a bona fide voltage sensor, was found to be voltage-independent.

    “Moreover, the recently characterized NALCN neuronal Na ϩ channel, which like CnCch1 has fewer positively charged amino acids (lysine and arginine) within its voltage-sensing S4 segment and thus lacks a bona fide voltage sensor, was found to be voltage-independent (38).”

    From Cch1 Restores Intracellular Ca2+ in Fungal Cells during Endoplasmic Reticulum Stress (2010) · cites this paper as [38]

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Authors
Lu, B., Su, Y., Das, S., Liu, J., Xia, J., & Ren, D.
Affiliations
University of Pennsylvania (US)
Corresponding author
Ren, Dejian
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2007-04
Volume
129
Issue
2
Pages
371-383
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2007.02.041
OpenAlex
W2064280886
Cited by
381
References
44
Citations by year
2026: 8 · 2025: 18 · 2024: 30 · 2023: 37 · 2022: 19 · 2021: 39 · 2020: 31 · 2019: 24 · 2018: 19 · 2017: 15 · 2016: 16 · 2015: 16 · 2014: 10 · 2013: 20 · 2012: 15
FWCI
6.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
NALCN, respiratory rhythm, non-selective cation channels, neuronal excitability, mouse mutants, hippocampal neurons, resting membrane potential
MeSH terms
Amino Acid Sequence, Animals, Animals, Newborn, Calcium, Cell Line, Central Nervous System, Cesium, Embryo, Mammalian, Embryo, Nonmammalian, Genes, Lethal, Hippocampus, Humans, Ion Channels, Membrane Potentials, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Potassium, Respiration, Sodium, Tetrodotoxin, Transfection, Xenopus, Sequence Alignment, DNA, Complementary, Mice, Knockout, Mice, Rats

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