Elevated intracellular Na + concentrations in developing spinal neurons

J Neurochem. 2017 Mar;140(5):755-765. doi: 10.1111/jnc.13936. Epub 2017 Jan 23.


Over 25 years ago it was first reported that intracellular chloride levels (Cl-in ) were higher in developing neurons than in maturity. This finding has had significant implications for understanding the excitability of developing networks and recognizing the underlying causes of hyperexcitability associated with disease and neural injury. While there is some evidence that intracellular sodium levels (Na+in ) change during the development of non-neural cells, it has largely been assumed that Na+in is the same in developing and mature neurons. Here, using the sodium indicator SBFI, we test this idea and find that Na+in is significantly higher in embryonic spinal motoneurons and interneurons than in maturity. We find that Na+in reaches ~ 60 mM in mid-embryonic development and is then reduced to ~ 30 mM in late embryonic development. By retrogradely labeling motoneurons with SBFI we can reliably follow Na+in levels in vitro for hours. Bursts of spiking activity, and blocking voltage-gated sodium channels did not influence observed motoneuron sodium levels. On the other hand, Na+in was reduced by blocking the Na+ -K+ -2Cl- cotransporter NKCC1, and was highly sensitive to changes in external Na+ and a blocker of the Na+ /K+ ATPase. Our findings suggest that the Na+ gradient is weaker in embryonic neuronal development and strengthens in maturity in a manner similar to that of Cl- .

Keywords: SBFI; ATPase; chick embryo; ionic gradient; sodium.

MeSH terms

  • Animals
  • Benzofurans
  • Chick Embryo
  • Chickens
  • Chlorides / metabolism
  • Embryonic Development
  • Ethers, Cyclic
  • Interneurons / metabolism
  • Intracellular Space / metabolism*
  • Motor Neurons / metabolism
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Sodium / metabolism*
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Spinal Cord / embryology
  • Spinal Cord / growth & development*
  • Spinal Cord / metabolism*


  • Benzofurans
  • Chlorides
  • Ethers, Cyclic
  • sodium-binding benzofuran isophthalate
  • Sodium
  • Sodium-Potassium-Exchanging ATPase