Proc Natl Acad Sci U S A. 2004 May 25;101(21):8168-73. Epub 2004 May
Craner MJ, Newcombe J, Black JA, Hartle C, Cuzner ML, Waxman SG.
Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale School of Medicine, New Haven, CT 06510.
Although voltage-gated sodium channels are known to be deployed along experimentally demyelinated axons, the molecular identities of the sodium channels expressed along axons in human demyelinating diseases such as multiple sclerosis (MS) have not been determined.
Here we demonstrate changes in the expression of sodium channels in demyelinated axons in MS, with Na(v)1.6 confined to nodes of Ranvier in controls but with diffuse distribution of Na(v)1.2 and Na(v)1.6 along extensive regions of demyelinated axons within acute MS plaques.
Using triple-labeled fluorescent immunocytochemistry, we also show that Na(v)1.6, which is known to produce a persistent sodium current, and the Na(+)/Ca(2+) exchanger, which can be driven by persistent sodium current to import damaging levels of calcium into axons, are colocalized with beta-amyloid precursor protein, a marker of axonal injury, in acute MS lesions.
Our results demonstrate the molecular identities of the sodium channels expressed along demyelinated and degenerating axons in MS and suggest that coexpression of Na(v)1.6 and Na(+)/Ca(2+) exchanger is associated with axonal degeneration in MS.