At the nodes of Ranvier, excitable axon membranes are exposed directly to the extracellular fluid. Cations are accumulated and depleted in the local extracellular nodal region during action potential propagation, but the impact of the extranodal micromilieu on signal propagation still remains unclear. Brain-specific hyaluronan-binding link protein, Bral1, colocalizes and forms complexes with negatively charged extracellular matrix (ECM) proteins, such as versican V2 and brevican, at the nodes of Ranvier in the myelinated white matter. The link protein family, including Bral1, appears to be the linchpin of these hyaluronan-bound ECM complexes. Here we report that the hyaluronan-associated ECM no longer shows a nodal pattern and that CNS nerve conduction is markedly decreased in Bral1-deficient mice even though there were no differences between wild-type and mutant mice in the clustering or transition of ion channels at the nodes or in the tissue morphology around the nodes of Ranvier. However, changes in the extracellular space diffusion parameters, measured by the real-time iontophoretic method and diffusion-weighted magnetic resonance imaging (MRI), suggest a reduction in the diffusion hindrances in the white matter of mutant mice. These findings provide a better understanding of the mechanisms underlying the accumulation of cations due to diffusion barriers around the nodes during saltatory conduction, which further implies the importance of the Bral1-based extramilieu for neuronal conductivity.
- MeSH
- akční potenciály * fyziologie MeSH
- buněčná membrána metabolismus MeSH
- centrální nervový systém * metabolismus ultrastruktura MeSH
- difuze MeSH
- difuzní magnetická rezonance MeSH
- extracelulární matrix metabolismus MeSH
- gating iontového kanálu fyziologie MeSH
- iontové kanály metabolismus MeSH
- kationty metabolismus MeSH
- kyselina hyaluronová metabolismus MeSH
- myši inbrední ICR MeSH
- myši knockoutované MeSH
- myši MeSH
- nervová vlákna myelinizovaná * metabolismus ultrastruktura MeSH
- nervové vedení * fyziologie MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- proteoglykany genetika metabolismus MeSH
- Ranvierovy zářezy * metabolismus ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
