Support of Nerve Conduction by Respiring Myelin Sheath: Role of Connexons

Mol Neurobiol. 2016 May;53(4):2468-79. doi: 10.1007/s12035-015-9216-0. Epub 2015 Jun 2.


Recently, we have demonstrated that myelin conducts an extramitochondrial oxidative phosphorylation, hypothesizing a novel supportive role for myelin in favor of the axon. We have also hypothesized that the ATP produced in myelin could be transferred thought gap junctions. In this work, by biochemical, immunohistochemical, and electrophysiological techniques, the existence of a connection among myelin to the axon was evaluated, to understand how ATP could be transferred from sheath to the axoplasm. Data confirm a functional expression of oxidative phosphorylation in isolated myelin. Moreover, WB and immunohistochemistry on optic nerve slices show that connexins 32 and 43 are present in myelin and colocalize with myelin basic protein. Interestingly, addition of carbenoxolone or oleamide, two gap junction blockers, causes a decrease in oxidative metabolism in purified myelin, but not in mitochondria. Similar effects were observed on conduction speed in hippocampal Schaffer collateral, in the presence of oleamide. Confocal analysis of optic nerve slices showed that lucifer yellow (that only passes through aqueous pores) signal was found in both the sheath layers and the axoplasma. In the presence of oleamide, but not with oleic acid, signal significantly decreased in the sheath and was lost inside the axon. This suggests the existence of a link among myelin and axons. These results, while supporting the idea that ATP aerobically synthesized in myelin sheath could be transferred to the axoplasm through gap junctions, shed new light on the function of the sheath.

Keywords: Connexins; Extramitochondrial ATP production; Gap junction; Nervous system metabolism; OXPHOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Respiration
  • Connectome*
  • Connexins / metabolism
  • Energy Metabolism
  • Gap Junctions / metabolism
  • Hippocampus / pathology
  • Immunohistochemistry
  • Male
  • Mice, Inbred ICR
  • Mitochondria / metabolism
  • Myelin Sheath / metabolism*
  • Neural Conduction*
  • Oxidative Phosphorylation
  • Oxygen Consumption


  • Connexins
  • Adenosine Triphosphate