Neurotherapeutics

, Volume 14, Issue 1, pp 78–90

Axonal Excitability in Amyotrophic Lateral Sclerosis

Axonal Excitability in ALS
  • Susanna B. Park
  • Matthew C. Kiernan
  • Steve Vucic
Review

DOI: 10.1007/s13311-016-0492-9

Cite this article as:
Park, S.B., Kiernan, M.C. & Vucic, S. Neurotherapeutics (2017) 14: 78. doi:10.1007/s13311-016-0492-9

Abstract

Axonal excitability testing provides in vivo assessment of axonal ion channel function and membrane potential. Excitability techniques have provided insights into the pathophysiological mechanisms underlying the development of neurodegeneration and clinical features of amyotrophic lateral sclerosis (ALS) and related neuromuscular disorders. Specifically, abnormalities of Na+ and K+ conductances contribute to development of membrane hyperexcitability in ALS, thereby leading to symptom generation of muscle cramps and fasciculations, in addition to promoting a neurodegenerative cascade via Ca2+-mediated processes. Modulation of axonal ion channel function in ALS has resulted in significant symptomatic improvement that has been accompanied by stabilization of axonal excitability parameters. Separately, axonal ion channel dysfunction evolves with disease progression and correlates with survival, thereby serving as a potential therapeutic biomarker in ALS. The present review provides an overview of axonal excitability techniques and the physiological mechanisms underlying membrane excitability, with a focus on the role of axonal ion channel dysfunction in motor neuron disease and related neuromuscular diseases.

Keywords

Amyotrophic lateral sclerosis axonal excitability hyperexcitability neuromuscular disorders ion channels neurodegeneration 

Supplementary material

13311_2016_492_MOESM1_ESM.pdf (1.2 mb)
ESM 1(PDF 1224 kb)

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2016

Authors and Affiliations

  • Susanna B. Park
    • 1
  • Matthew C. Kiernan
    • 1
  • Steve Vucic
    • 2
  1. 1.Brain and Mind CentreUniversity of SydneySydneyAustralia
  2. 2.Westmead Clinical SchoolUniversity of SydneySydneyAustralia

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