Genetic and physiological evidence that oligodendrocyte gap junctions contribute to spatial buffering of potassium released during neuronal activity

Daniela M. Menichella, Marta Majdan, Rajeshwar Awatramani, Daniel A. Goodenough, Erich Sirkowski, Steven S. Scherer, David L. Paul*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Mice lacking the K+ channel Kir4.1 or both connexin32 (Cx32) and Cx47 exhibit myelin-associated vacuoles, raising the possibility that oligodendrocytes, and the connexins they express, contribute to recycling the K+ evolved during neuronal activity. To study this possibility, we first examined the effect of neuronal activity on the appearance of vacuoles in mice lacking both Cx32 and Cx47. The size and number of myelin vacuoles was dramatically increased when axonal activity was increased, by either a natural stimulus (eye opening) or pharmacological treatment. Conversely, myelin vacuoles were dramatically reduced when axonal activity was suppressed. Second, we used genetic complementation to test for a relationship between the function of Kir4.1 and oligodendrocyte connexins. In a Cx32-null background, haploinsufficiency of either Cx47 or Kir4.1 did not affect myelin, but double heterozygotes developed vacuoles, consistent with the idea that oligodendrocyte connexins and Kir4.1 function in a common pathway. Together, these results implicate oligodendrocytes and their connexins as having critical roles in the buffering of K+ released during neuronal activity.

Original languageEnglish (US)
Pages (from-to)10984-10991
Number of pages8
JournalJournal of Neuroscience
Volume26
Issue number43
DOIs
StatePublished - Oct 25 2006

Keywords

  • Astrocyte
  • Connexin
  • Demyelination
  • Gap junction
  • Oligodendrocyte
  • Potassium channel

ASJC Scopus subject areas

  • Neuroscience(all)

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