Genetic and physiological evidence that oligodendrocyte gap junctions contribute to spatial buffering of potassium released during neuronal activity.
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.
Menichella
Daniela M
DM
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Majdan
Marta
M
Awatramani
Rajeshwar
R
Goodenough
Daniel A
DA
Sirkowski
Erich
E
Scherer
Steven S
SS
Paul
David L
DL
D000818:Animals; D005260:Female; D017629:Gap Junctions / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D000098854:Kcnj10 Channel
D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium