Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

J Cell Sci. 2016 May 1;129(9):1902-14. doi: 10.1242/jcs.178731. Epub 2016 Mar 22.

Abstract

Oligodendrocyte precursor cells (OPCs) undergo a series of energy-consuming developmental events; however, the uptake and trafficking pathways for their energy metabolites remain unknown. In the present study, we found that 2-NBDG, a fluorescent glucose analog, can be delivered between astrocytes and oligodendrocytes through connexin-based gap junction channels but cannot be transferred between astrocytes and OPCs. Instead, connexin hemichannel-mediated glucose uptake supports OPC proliferation, and ethidium bromide uptake or increase of 2-NBDG uptake rate is correlated with intracellular Ca(2+) elevation in OPCs, indicating a Ca(2+)-dependent activation of connexin hemichannels. Interestingly, deletion of connexin 43 (Cx43, also known as GJA1) in astrocytes inhibits OPC proliferation by decreasing matrix glucose levels without impacting on OPC hemichannel properties, a process that also occurs in corpus callosum from acute brain slices. Thus, dual functions of connexin-based channels contribute to glucose supply in oligodendroglial lineage, which might pave a new way for energy-metabolism-directed oligodendroglial-targeted therapies.

Keywords: Connexin hemichannel; Glial metabolism; Glucose uptake; Intracellular Ca2+; Oligodendroglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Corpus Callosum / cytology
  • Corpus Callosum / metabolism*
  • Glucose / genetics
  • Glucose / metabolism
  • Mice
  • Mice, Knockout
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*

Substances

  • Connexin 43
  • GJA1 protein, mouse
  • Glucose
  • Calcium