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Excitability properties of mouse and human skeletal muscle fibres compared by muscle velocity recovery cycles

Lookup NU author(s): Dr Karen SuetterlinORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Mouse models of skeletal muscle channelopathies are not phenocopies of human disease. In some cases (e.g. Myotonia Congenita) the phenotype is much more severe, whilst in others (e.g. Hypokalaemic periodic paralysis) rodent physiology is protective. This suggests a species’ difference in muscle excitability properties. In humans these can be measured indirectly by the post-impulse changes in conduction velocity, using Muscle Velocity Recovery Cycles (MVRCs). We performed MVRCs in mice and compared their muscle excitability properties with humans. Mouse Tibialis Anterior MVRCs (n = 70) have only one phase of supernormality (increased conduction velocity), which is smaller in magnitude (p = 9 × 10−21), and shorter in duration (p = 3 × 10−24) than human (n = 26). This abbreviated supernormality is followed by a period of late subnormality (reduced velocity) in mice, which overlaps in time with the late supernormality seen in human MVRCs. The period of late subnormality suggests increased t-tubule Na+/K+-pump activity. The subnormal phase in mice was converted to supernormality by blocking ClC-1 chloride channels, suggesting relatively higher chloride conductance in skeletal muscle. Our findings help explain discrepancies in phenotype between mice and humans with skeletal muscle channelopathies and potentially other neuromuscular disorders. MVRCs are a valuable new tool to compare in vivo muscle membrane properties between species and will allow further dissection of the molecular mechanisms regulating muscle excitability.

Publication metadata

Author(s): Suetterlin KJ, Männikkö R, Matthews E, Greensmith L, Hanna MG, Bostock H, Tan SV

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2022

Volume: 32

Issue: 4

Pages: 347-345

Print publication date: 01/04/2022

Online publication date: 26/02/2022

Acceptance date: 22/02/2022

Date deposited: 26/06/2023

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elseiver


DOI: 10.1016/j.nmd.2022.02.011


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Funder referenceFunder name
Brain Research UK
Wellcome Trust
UCLH NIHR Biomedical Research Centre