title: Axonal Excitability in Amyotrophic Lateral Sclerosis : Axonal Excitability in ALS.
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.
authors.affiliation: Brain and Mind Centre, University of Sydney, Sydney, Australia.
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.affiliation: Brain and Mind Centre, University of Sydney, Sydney, Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
authors.affiliation: Westmead Clinical School, University of Sydney, Sydney, Australia. steve.vucic@sydney.edu.au.
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000503:physiopathology*; D001369:Axons / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D008564:Membrane Potentials; D015221:Potassium Channels / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology
chemical_list: D015221:Potassium Channels; D015222:Sodium Channels
keywords: Amyotrophic lateral sclerosis; axonal excitability; hyperexcitability; ion channels; neurodegeneration; neuromuscular disorders