K+ channels are differentially expressed throughout oligodendrocyte (Olg) development. KV1 family voltage-sensitive K+ channels have been implicated in proliferation and migration of Olg progenitor cell (OPC) stage, and inward rectifier K+ channels (K IR)4.1 are required for OPC differentiation to myelin-forming Olg. In this report we have identified a Shaw family K+ channel, K V3.1, that is involved in proliferation and migration of OPC and axon myelination. Application of anti-KV3.1 antibody or knockout of Kv3.1 gene decreased the sustained K+ current component of OPC by 50% and 75%, respectively. In functional assays block of KV3.1-specific currents or knockout of Kv3.1 gene inhibited proliferation and migration of OPC. Adult Kv3.1 gene-knockout mice had decreased diameter of axons and decreased thickness of myelin in optic nerves compared with age-matched wild-type littermates. Additionally, KV3.1 was identified as an associated protein of Olg-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 Olg lineage and, in association with OSP/claudin-11, plays a significant role in OPC proliferation and migration and myelination of axons.
All Science Journal Classification (ASJC) codes
- Cell Biology