K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development

K+ channels are differentially expressed throughout oligodendrocyte (O1g) development. K(V)1 family voltage-sensitive K+ channels have been implicated in proliferation and migration of O1g progenitor cell (OPC) stage, and inward rectifier K+ channels (K-IR) 4.1 are required for OPC differentiation to myelin-forming O1g. In this report we have identified a Shaw family K+ channel, K(V)3.1, that is involved in proliferation and migration of OPC and axon myelination. Application of anti-K(V)3.1 antibody or knockout of K(V)3.1 gene decreased the sustained K+ current component of OPC by 50% and 75%, respectively. In functional assays block of K(V)3.1-specific currents or knockout of K(V)3.1 gene inhibited proliferation and migration of OPC. Adult K(V)3.1 gene-knockout mice had decreased diameter of axons and decreased thickness of myelin in optic nerves compared with age-matched wild-type littermates. Additionally, K(V)3.1 was identified as an associated protein of O1g-specific protein (OSP)/claudin-11 via yeast two-hybrid analysis, which was confirmed by coimmunoprecipitation and coimmunohistochemistry. In summary, the KV3.1 K+ current accounts for a significant component of the total K+ current in cells of the O1g lineage and, in association with OSP/claudin-11, plays a significant role in OPC proliferation and migration and myelination of axons.