Journal Article

Up-regulation of slow K<sup>+</sup> channels in peripheral motor axons: a transcriptional channelopathy in multiple sclerosis

Karl Ng, James Howells, John D. Pollard and David Burke

in Brain

Published on behalf of The Guarantors of Brain

Volume 131, issue 11, pages 3062-3071
Published in print November 2008 | ISSN: 0006-8950
Published online August 2008 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awn180
Up-regulation of slow K+ channels in peripheral motor axons: a transcriptional channelopathy in multiple sclerosis

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Spinal lesions produce plastic changes in motoneuron properties. We have documented the excitability of motor axons in the median nerve of 12 patients with multiple sclerosis and 50 normal subjects, hypothesizing that plastic changes in the properties of spinal motoneurons might be reflected in the properties of peripheral motor axons and be demonstrable in vivo. In the patients, there were changes in physiological measures of axonal excitability attributable to increased slow K+ channel activity. Other measures were within control limits. These changes could be modelled by an 11% increase in slow K+ current, with compensatory changes in membrane potential, suggesting increased expression of the responsible channels. The changes cannot be explained solely by changes in membrane potential and are not those expected if peripheral nerve axons were involved in the inflammatory process of multiple sclerosis. They probably represent a transcriptional channelopathy, due to up-regulation of channel expression. The abnormalities do not imply that peripheral nerve function has been significantly compromised, but they do suggest that the properties of the parent motoneurons have changed. This study thus provides evidence for plasticity in motoneuronal properties at a molecular level, the first such evidence for intact human subjects.

Keywords: slow K channel; multiple sclerosis; motoneuron; channelopathy; plasticity

Journal Article.  6894 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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