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Development of a model for microphysiological simulations

Development of a model for microphysiological simulations The node of Ranvier is a complex structure found along myelinated nerves of vertebrate animals. Specific membrane, cytoskeletal, junctional, extracellular matrix proteins and organelles interact to maintain and regulate associated ion movements between spaces in the nodal complex, potentially influencing response variation during repetitive activations or metabolic stress. Understanding and building high resolution three dimensional (3D) structures of the node of Ranvier, including localization of specific macromolecules, is crucial to a better understanding of the relationship between its structure and function and the macromolecular basis for impaired conduction in disease. Using serial section electron tomographic methods, we have constructed accurate 3D models of the nodal complex from mouse spinal roots with resolution better than 7.5nm. These reconstructed volumes contain 75–80% of the thickness of the nodal region. We also directly imaged the glial axonal junctions that serve to anchor the terminal loops of the myelin lamellae to the axolemma. We created a model of an intact node of Ranvier by truncating the volume at its mid-point in Z, duplicating the remaining volume and then merging the new half volume with mirror symmetry about the Z-axis. We added to this model the distribution and number of Na+ channels on this reconstruction using tools associated with the MCell simulation program environment. The model created provides accurate structural descriptions of the membrane compartments, external spaces, and formed structures enabling more realistic simulations of the role of the node in modulation of impulse propagation than have been conducted on myelinated nerve previously. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuroinformatics Springer Journals

Development of a model for microphysiological simulations

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Publisher
Springer Journals
Copyright
Copyright © 2005 by Humana Press Inc
Subject
Biomedicine; Neurosciences; Computer Appl. in Life Sciences; Neurology; Biotechnology; Computational Biology/Bioinformatics
ISSN
1539-2791
eISSN
1559-0089
DOI
10.1385/NI:3:2:133
pmid
15988042
Publisher site
See Article on Publisher Site

Abstract

The node of Ranvier is a complex structure found along myelinated nerves of vertebrate animals. Specific membrane, cytoskeletal, junctional, extracellular matrix proteins and organelles interact to maintain and regulate associated ion movements between spaces in the nodal complex, potentially influencing response variation during repetitive activations or metabolic stress. Understanding and building high resolution three dimensional (3D) structures of the node of Ranvier, including localization of specific macromolecules, is crucial to a better understanding of the relationship between its structure and function and the macromolecular basis for impaired conduction in disease. Using serial section electron tomographic methods, we have constructed accurate 3D models of the nodal complex from mouse spinal roots with resolution better than 7.5nm. These reconstructed volumes contain 75–80% of the thickness of the nodal region. We also directly imaged the glial axonal junctions that serve to anchor the terminal loops of the myelin lamellae to the axolemma. We created a model of an intact node of Ranvier by truncating the volume at its mid-point in Z, duplicating the remaining volume and then merging the new half volume with mirror symmetry about the Z-axis. We added to this model the distribution and number of Na+ channels on this reconstruction using tools associated with the MCell simulation program environment. The model created provides accurate structural descriptions of the membrane compartments, external spaces, and formed structures enabling more realistic simulations of the role of the node in modulation of impulse propagation than have been conducted on myelinated nerve previously.

Journal

Neuroinformatics – Springer Journals

Published: Jun 6, 2005

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