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Impaired Wheel Running Exercise in CLC-1 Chloride Channel-Deficient Myotonic Mice

By Erik van Lunteren, Michelle Moyer, Jessica Cooperrider and Jennifer Pollarine


Background: Genetic deficiency of the muscle CLC-1 chloride channel leads to myotonia, which is manifested most prominently by slowing of muscle relaxation. Humans experience this as muscle stiffness upon initiation of contraction, although this can be overcome with repeated efforts (the “warm-up” phenomenon). The extent to which CLC-1 deficiency impairs exercise activity is controversial. We hypothesized that skeletal muscle CLC-1 chloride channel deficiency leads to severe reductions in spontaneous exercise. Methodology/Principal Findings: To examine this quantitatively, myotonic CLC-1 deficient mice were provided access to running wheels, and their spontaneous running activity was quantified subsequently. Differences between myotonic and normal mice in running were not present soon after introduction to the running wheels, but were fully established during week 2. During the eighth week, myotonic mice were running significantly less than normal mice (322 ± 177 vs 5058 ± 1253 m/day, P = 0.025). Furthermore, there were considerable reductions in consecutive running times (18.8 ± 1.5 vs 59.0 ± 3.7 min, P < 0.001) and in the distance per consecutive running period (58 ± 38 vs 601 ± 174 m, P = 0.048) in myotonic compared with normal animals. Conclusion/Significance: These findings indicate that CLC-1 chloride deficient myotonia in mice markedly impairs spontaneous exercise activity, with reductions in both total distance and consecutive running times

Topics: Physiology
Publisher: Frontiers Research Foundation
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Provided by: PubMed Central

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  3. (1984). Calcium-binding protein, parvalbumin, is reduced in mutant mammalian muscle with abnormal contractile properties.
  4. (1975). Clinical and electrophysiological observations in patients with myotonic muscle disease and the therapeutic effect of N-propyl-ajmalin.
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  8. (2006). Emerging roles of chloride channels in human diseases.
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  10. (2011). Fatigue-inducing stimulation resolves myotonia in a drug-induced model.
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  13. (1993). Genetics and physiology of the myotonic muscle disorders.
  14. (2002). Genetics disorders of neuromuscular ion channels.
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  16. (1991). Inactivation of muscle chloride channel by transposon insertion in myotonic mice.
  17. (2007). Isotonic contractile impairment due to genetic CLC-1 chloride channel deficiency inmyotonicmousediaphragmmuscle.
  18. (1995). Modifications of gene expression in myotonicmurineskeletalmuscleare associatedwithabnormalexpression of myogenic regulatory factors.
  19. (1996). Molecular basis for decreased muscle chloride conductance in the myotonic goat.
  20. (2002). Myotonia caused by mutations in the muscle chloride channel gene CLCN1.
  21. (2001). Myotonia congenita:amusclediseaseconcealedby muscular physique.
  22. (1982). Myotonia, a new inherited muscle disease in mice.
  23. (1998). Myotonic ADR-MDX mutant mice show less severe muscular dystrophy than MDX mice.
  24. (2005). Phenotypic variability in myotonia congenita.
  25. (2005). Physiological functions of CLC Clchannels gleaned from human genetic disease and mouse models.
  26. (1991). Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel.
  27. (2005). Quantification of mobility impairment and selfassessment of stiffness in patients with myotonia congenita by the physiotherapist.
  28. (2004). Reduced amount and disrupted temporal pattern of spontaneous exercise in diabetic rats.
  29. (2002). Running endurance abnormality in mdx mice.
  30. (1988). The myotonic mouse mutant ADR: physiological and histochemical properties of muscle.
  31. (1988). The myotonic mouse mutantADR: electrophysiologyof themusclefiber.MuscleNerve 11,
  32. (1997). Unusual causes of stiffness in two hockey players.
  33. (1994). Voluntary exercise decreases progression ofmusculardystrophyindiaphragm of mdx mice.
  34. Wheel running exercise alters rat diaphragm action potentials and their regulation by K+ channels.