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The Journal of Neuroscience, June 1, 2003, 23(11):4509-4518

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Kv3.1b Is a Novel Component of CNS Nodes

Jérôme Devaux,1,6 Gisèle Alcaraz,2 Judith Grinspan,3 Vann Bennett,4 Rolf Joho,5 Marcel Crest,6 and Steven S. Scherer1

1 Department of Neurology, The University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6077, 2 Institut National de la Santé et de la Recherche Médicale Unité 464, Institut Jean Roche, Faculté de Médecine Nord, Université de la Méditerranée, 13916 Marseille Cedex 20, France, 3 Division of Neurology Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-6077, 4 Howard Hughes Medical Institute and Departments of Biochemistry and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, 5 Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, and 6 Laboratoire Intégration des Informations Sensorielles, Centre National de la Recherche Scientifique, 13402 Marseille Cedex 20, France

We herein demonstrate that Kv3.1b subunits are present at nodes of Ranvier in the CNS of both rats and mice. Kv3.1b colocalizes with voltage-gated Na+ channels in a subset of nodes in the spinal cord, particularly those of large myelinated axons. Kv3.1b is abundantly expressed in the gray matter of the spinal cord, but does not colocalize with Na+ channels in initial segments. In the PNS, few nodes are Kv3.1b-positive. During the development of the CNS, Kv3.1b clustering at nodes occurs later than that of Na+ channels, but precedes the juxtaparanodal clustering of Kv1.2. Moreover, in myelin-deficient rats, which have severe CNS dysmyelination, node-like clusters of Kv3.1b and Na+ channels are observed even in regions devoid of oligodendrocytes. Ankyrin G coimmunoprecipitates Kv3.1b in vivo, indicating that these two proteins may interact in the CNS at nodes. 4-Aminopyridine, a K+ channel blocker, broadened the compound action potential recorded from adult rat optic nerve and spinal cord, but not from the sciatic nerve. These effects were also observed in Kv3.1-deficient mice. In conclusion, Kv3.1b is the first K+ channel subunit to be identified in CNS nodes; but Kv3.1b does not account for the effects of 4-aminopyridine on central myelinated tracts.

Key words: Shaw; potassium channels; oligodendrocyte; Schwann cells; myelin; multiple sclerosis


Received Aug. 22, 2002; revised Feb. 21, 2003; accepted Mar. 12, 2003.




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