Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3113-3123 |
| Number of pages | 11 |
| Journal | Journal of Neuroscience |
| Volume | 30 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Feb 24 2010 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Bral1 : Its role in diffusion barrier formation and conduction velocity in the CNS. / Bekku, Yoko; Vargová, Lýdia; Goto, Yoshinobu; Vorísek, Ivan; Dmytrenko, Lesia; Narasaki, Masahiro; Ohtsuka, Aiji; Fässler, Reinhard; Ninomiya, Yoshifumi; Syková, Eva; Oohashi, Toshitaka.
In: Journal of Neuroscience, Vol. 30, No. 8, 24.02.2010, p. 3113-3123.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bral1
T2 - Its role in diffusion barrier formation and conduction velocity in the CNS
AU - Bekku, Yoko
AU - Vargová, Lýdia
AU - Goto, Yoshinobu
AU - Vorísek, Ivan
AU - Dmytrenko, Lesia
AU - Narasaki, Masahiro
AU - Ohtsuka, Aiji
AU - Fässler, Reinhard
AU - Ninomiya, Yoshifumi
AU - Syková, Eva
AU - Oohashi, Toshitaka
PY - 2010/2/24
Y1 - 2010/2/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77649119041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649119041&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5598-09.2010
DO - 10.1523/JNEUROSCI.5598-09.2010
M3 - Article
C2 - 20181608
AN - SCOPUS:77649119041
VL - 30
SP - 3113
EP - 3123
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 8
ER -