Oligodendrocyte-axon metabolic coupling is mediated by extracellular K⁺ and maintains axonal health.

ABSTRACT: The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and how rapid axon-OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca²⁺) and metabolite fluxes in the mouse optic nerve. We show that fast axonal spiking triggers Ca²⁺ signaling and glycolysis in OLs. OLs detect axonal activity through increases in extracellular potassium (K⁺) concentrations and activation of Kir4.1 channels, thereby regulating metabolite supply to axons. Both pharmacological inhibition and OL-specific inactivation of Kir4.1 reduce the activity-induced axonal lactate surge. Mice lacking oligodendroglial Kir4.1 exhibit lower resting lactate levels and altered gl

SUBMITTER: Looser ZJ 

PROVIDER: S-EPMC10917689 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature