title: Up-regulation of slow K(+) channels in peripheral motor axons: a transcriptional channelopathy in multiple sclerosis.
abstract: 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.
authors.affiliation: Institute of Clinical Neurosciences, Royal Prince Alfred Hospital and The University of Sydney, Sydney, NSW, Australia. kng@med.usyd.edu.au
authors.forename: Karl
authors.initials: K
authors.lastname: Ng
authors.forename: James
authors.initials: J
authors.lastname: Howells
authors.forename: John D
authors.initials: JD
authors.lastname: Pollard
authors.forename: David
authors.initials: D
authors.lastname: Burke
mesh_terms: D000328:Adult; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008564:Membrane Potentials; D008875:Middle Aged; D008959:Models, Neurological; D009046:Motor Neurons / Q000378:metabolism* / Q000502:physiology; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000503:physiopathology; D009431:Neural Conduction; D009473:Neuronal Plasticity; D015221:Potassium Channels / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015221:Potassium Channels