Submitted on October 12, 2005
Accepted on April 12, 2006
K+ channel Kv3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development
Seema K Tiwari-Woodruff1*, Luis Beltran-Parrazal2, Andrew Charles2, Thomas Keck2, Trung Vu2, and Jeff Bronstein2
1 Neurology, UCLA Multiple Sclerosis Program, Los Angeles, California, United States; Neurolgy, David Geffen School of Medicine, Los Angeles, California, United States
2 Neurolgy, David Geffen School of Medicine, Los Angeles, California, United States
* To whom correspondence should be addressed. E-mail: seemaw{at}ucla.edu.
Potassium (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 Kir4.1 are required for OPC differentiation to myelin forming OLGs. In this report we have identified a Shaw family K+ channel, Kv3.1 that is involved in proliferation and migration of OPCs and axon myelination. Application of anti-Kv3.1 antibody or knocking out Kv3.1 gene decreased the sustained K+ current component of OPCs by 50% and 75% respectively. In functional assays blocking Kv3.1 specific currents or knocking out Kv3.1 gene inhibit proliferation and migration of OPCs. Adult Kv3.1 gene knockout mice had decreased diameter of axons and decreased thickness of myelin in optic nerves compared to age matched wild-type littermates. Additionally, Kv3.1 was identified as an associated protein of OSP/claudin-11 via yeast two-hybrid analysis, which was confirmed, by co-immunoprecipitation and co-immunohistochemistry. 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, migration, and myelination of axons.
