Saltatory conduction in mammalian myelinated axons was thought to be well understood before recent discoveries revealed unexpected subcellular distributions and molecular identities of the K+-conductance pathways that provide for rapid axonal repolarization. Here, we visualize, identify, localize, quantify, and ultrastructurally-characterize axonal KV1.1/KV1.2 channels in sciatic nerves of rodents. Using light-microscopic immunocytochemistry and freeze-fracture-replica immunogold labeling electron microscopy, KV1.1/KV1.2 channels are localized to three anatomically- and compositionally-distinct domains in the internodal axolemmas of large myelinated axons, where they form densely-packed "rosettes" of 9 nm intramembrane particles. These axolemmal KV1.1/KV1.2 rosettes are precisely aligned with and ultrastructurally-coupled to Cx29 channels, also in matching rosettes, in the surrounding juxtaparanodal myelin collars and along the inner mesaxon. As >98% of transmembrane proteins large enough to represent ion channels in these specialized domains, ~500,000 KV1.1/KV1.2 channels define the paired juxtaparanodal regions as exclusive membrane domains for the voltage-gated K+ conductance that underlies rapid axonal repolarization in mammals. The 1:1 molecular linkage of KV1 channels to Cx29 channels in the apposed juxtaparanodal collars, plus their linkage to an additional 250,000-400,000 Cx29 channels along each inner mesaxon in every large-diameter myelinated axon examined, support previously-proposed K+ conductance directly from juxtaparanodal axoplasm into juxtaparanodal myeloplasm in mammalian axons. With neither Cx29 protein nor myelin rosettes detectable in frog myelinated axons, these data showing axon-to-myelin linkage by abundant KV1/Cx29 channels in rodent axons support renewed consideration of an electrically-active role for myelin in increasing both saltatory conduction velocity and maximum propagation frequency in mammalian myelinated axons.
- connexin-29 channels
- inner mesaxon
- Kv1.1/Kv1.2 channels
- Copyright © 2015, Journal of Neurophysiology