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

Cell. 2007 Apr 20;129(2):371-83. doi: 10.1016/j.cell.2007.02.041.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Cell Line
  • Central Nervous System / cytology
  • Cesium / pharmacology
  • DNA, Complementary
  • Embryo, Mammalian / metabolism
  • Embryo, Nonmammalian
  • Genes, Lethal
  • Hippocampus / cytology
  • Humans
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Membrane Potentials
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Potassium / metabolism
  • Rats
  • Respiration*
  • Sequence Alignment
  • Sodium / metabolism*
  • Tetrodotoxin / pharmacology
  • Transfection
  • Xenopus

Substances

  • DNA, Complementary
  • Ion Channels
  • NALCN protein, mouse
  • Nerve Tissue Proteins
  • Cesium
  • Tetrodotoxin
  • Sodium
  • Potassium
  • Calcium