title: Chloride channels in myotonia congenita assessed by velocity recovery cycles.
abstract: BACKGROUND
  Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC-1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected.
  
  
  METHODS
  MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched, normal controls.
  
  
  RESULTS
  MC patients exhibited increased early supernormality, but this was prevented by treatment with sodium channel blockers. After multiple conditioning stimuli, late supernormality was enhanced in all MC patients, indicating delayed repolarization. These abnormalities were similar between the MC subtypes, but recessive patients showed a greater drop in amplitude during repetitive stimulation.
  
  
  CONCLUSIONS
  MVRCs indicate that chloride conductance only becomes important when muscle fibers are depolarized. The differential responses to repetitive stimulation suggest that, in dominant MC, the affected chloride channels are activated by strong depolarization, consistent with a positive shift of the CLC-1 activation curve.
authors.affiliation: MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK; Department of Genetics, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK; Department of Neurology and Neurophysiology, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: S Veronica
authors.initials: SV
authors.lastname: Tan
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Z'Graggen
authors.forename: Delphine
authors.initials: D
authors.lastname: Boërio
authors.forename: Dipa Raja
authors.initials: DR
authors.lastname: Rayan
authors.forename: Fiona
authors.initials: F
authors.lastname: Norwood
authors.forename: Deborah
authors.initials: D
authors.lastname: Ruddy
authors.forename: R
authors.initials: R
authors.lastname: Howard
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.forename: Hugh
authors.initials: H
authors.lastname: Bostock
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018118:Chloride Channels / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology*; D009224:Myotonia Congenita / Q000188:drug therapy / Q000503:physiopathology*; D011930:Reaction Time / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D018118:Chloride Channels; D026941:Sodium Channel Blockers
keywords: chloride channels; muscle membrane potential; muscle velocity recovery cycle; myotonia congenita; tibialis anterior muscle