a1 Center for Molecular Medicine and Genetics
a2 Carman and Ann Adams Department of Pediatrics
a3 Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
a4 Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, PA, USA
a5 Département Signalisation Neuronale CRN2M, UMR 6231, CNRS, Université de la Méditerranée-Université Paul Cézanne, IFR Jean Roche Marseille, France
The insulative properties of myelin sheaths in the central and peripheral nervous systems (CNS and PNS) are widely thought to derive from the high resistance and low capacitance of the constituent membranes. Although this view adequately accounts for myelin function in large diameter fibers, it poorly reflects the behavior of small fibers that are prominent in many regions of the CNS. Herein, we develop a computational model to more accurately represent conduction in small fibers. By incorporating structural features that, hitherto, have not been simulated, we demonstrate that myelin tight junctions (TJs) improve saltatory conduction by reducing current flow through the myelin, limiting axonal membrane depolarization and restraining the activation of ion channels beneath the myelin sheath. Accordingly, our simulations provide a novel view of myelin by which TJs minimize charging of the membrane capacitance and lower the membrane time constant to improve the speed and accuracy of transmission in small diameter fibers. This study establishes possible mechanisms whereby TJs affect conduction in the absence of overt perturbations to myelin architecture and may in part explain the tremor and gait abnormalities observed in Claudin 11-null mice.
c1 Correspondence should be addressed to: Alexander Gow Center for Molecular Medicine and Genetics, 3216 Scott Hall 540 E Canfield Avenue, Wayne State University School of Medicine Detroit, MI 48201, USA phone: (313) 577-9401 Fax: (313) 577-1632 email: firstname.lastname@example.org