Markedly reduced axonal potassium channel expression in human sporadic amyotrophic lateral sclerosis: an immunohistochemical study.

Abstract

Fasciculations are characteristic features of amyotrophic lateral sclerosis (ALS), suggesting abnormally increased excitability of motor axons. Previous nerve excitability studies have shown reduced axonal potassium currents in ALS patients that may contribute to the hyperexcitability and thereby generation of fasciculations. To clarify changes in axonal ion channel expression in motor axons of ALS, we performed immunohistochemistry of potassium and sodium channels in the C7 and L5 ventral/dorsal roots obtained from five autopsy cases of sporadic ALS. Compared to controls, the immunoreactivity of potassium channels (Kv1.2) was markedly reduced in the ventral roots, but normal in the dorsal roots of all the ALS patients. Nodal sodium channel expression was not significantly different in ALS patients and control subjects. Our results show prominently reduced expression of axonal potassium channels, and provide the neuropathological and biological basis for decreased accommodative potassium currents in motor axons of ALS patients. The axonal hyperexcitability would lead to generation of fasciculations, and possibly enhances motor neuron death in ALS.

• Authors: Kazumoto Shibuya, Sonoko Misawa, Kimihito Arai, Miho Nakata, Kazuaki Kanai, Yasumasa Yoshiyama, Kimiko Ito, Sagiri Isose, Yu-ichi Noto, Saiko Nasu, Yukari Sekiguchi, Yumi Fujimaki, Shigeki Ohmori, Hiroshi Kitamura, Yasunori Sato, Satoshi Kuwabara
• Journal: Experimental neurology (Exp Neurol) Vol. 232 Issue 2 Pg. 149-53 (Dec 2011) ISSN: 1090-2430 [Electronic] United States
• PMID: 21906595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Kv1.2 Potassium Channel
• Sodium Channels

Topics

• Aged
• Aged, 80 and over
• Amyotrophic Lateral Sclerosis (metabolism, pathology)
• Axons (metabolism, pathology)
• Fasciculation (metabolism, pathology)
• Female
• Humans
• Immunohistochemistry
• Kv1.2 Potassium Channel (metabolism)
• Male
• Middle Aged
• Motor Neurons (metabolism, pathology)
• Receptor Aggregation (physiology)
• Sodium Channels (metabolism)
• Spinal Nerve Roots (metabolism)