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Neuroinformatics

, Volume 3, Issue 2, pp 133–162 | Cite as

Development of a model for microphysiological simulations

Small nodes of ranvier from peripheral nerves of mice reconstructed by electron tomography
  • Gina E. SosinskyEmail author
  • Thomas J. Deerinck
  • Rocco Greco
  • Casey H. Buitenhuys
  • Thomas M. Bartol
  • Mark H. EllismanEmail author
Original Article

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.

Index Entries

Myelinated axons peripheral nerve structure saltatory conduction ionic transmission three-dimensional reconstruction electron microscopy cell-cell junctions, axonal-glial interactions high pressure freezing 

Abbreviations

PNS

peripheral nervous system

CNS

central nervous system

HPF

high pressure freezing

EMT

electron microscopic tomography

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Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Gina E. Sosinsky
    • 1
    Email author
  • Thomas J. Deerinck
    • 1
  • Rocco Greco
    • 1
  • Casey H. Buitenhuys
    • 1
  • Thomas M. Bartol
    • 2
  • Mark H. Ellisman
    • 1
    Email author
  1. 1.National Center for Microscopy and Imaging Research, Department of Neurosciences and the Center for Research on Biological SystemsUniversity of CaliforniaSan Diego
  2. 2.Computational Neurobiology LaboratorySalk InstituteLa Jolla

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