Kv3.1b is a novel component of CNS nodes.
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.
Devaux
Jérôme
J
Department of Neurology, The University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6077, USA. jdevaux@mail.med.upenn.edu
Alcaraz
Gisèle
G
Grinspan
Judith
J
Bennett
Vann
V
Joho
Rolf
R
Crest
Marcel
M
Scherer
Steven S
SS
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D051662:Kv1.1 Potassium Channel; D051663:Kv1.2 Potassium Channel; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009479:Neuropeptides / Q000096:biosynthesis; D009836:Oligodendroglia; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011233:Precipitin Tests; D021122:Protein Subunits / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D051670:Shaw Potassium Channels; D015222:Sodium Channels / Q000378:metabolism
C094681:Ank3 protein, mouse; C490614:Ank3 protein, rat; D017487:Ankyrins; C496947:Kcna1 protein, mouse; C496970:Kcna2 protein, mouse; C496972:Kcna2 protein, rat; C490839:Kcnc1 protein, mouse; D051663:Kv1.2 Potassium Channel; D009479:Neuropeptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051670:Shaw Potassium Channels; D015222:Sodium Channels; D051662:Kv1.1 Potassium Channel; D015761:4-Aminopyridine