(A) Organization of the specialized axonal domains and oligodendroglial myelin wrapping that flanks the node of Ranvier, including the paranode, juxtaparanode, and internode. (B) Neuronal excitability is regulated by outward-rectifying axonal Kv7 potassium channels at the nodes of Ranvier. Inward-rectifying Kir4.1 potassium channels expressed by OLs are localized to the inner tongue, outer tongue, and paranodal loops. Healthy OLs in normal conditions vacuum up the increased extracellular potassium that is released by neuronal activity. Kapell, Fazio, and colleagues report that inflammatory demyelinating conditions result in dysfunction of this neuroglial potassium shuttling mechanism, with downregulation of neuronal Kv7 channels and oligodendroglial Kir4.1 channels. The authors’ findings suggest that targeting potassium channel function to normalize neuronal excitability may prevent neurodegeneration and promote the recovery of function.