title: Nongenomic actions of progesterone and 17β-estradiol on the chloride conductance of skeletal muscle.
abstract: BACKGROUND
  Myotonia congenita, caused by mutations in ClC-1, tends to be more severe in men and is often exacerbated by pregnancy.
  
  
  METHODS
  We performed whole-cell patch clamp of mouse muscle chloride currents in the absence/presence of 100 μM progesterone or 17β-estradiol.
  
  
  RESULTS
  100 μM progesterone rapidly and reversibly shifted the ClC-1 activation curve of mouse skeletal muscle (V50 changed from -52.6 ± 9.3 to +35.5 ± 6.7; P < 0.01) and markedly reduced chloride currents at depolarized potentials. 17β-estradiol at the same concentration had a similar but smaller effect (V50 change from -57.2 ± 7.6 to -40.5 ± 9.8; P < 0.05). 1 μM progesterone produced no significant effect.
  
  
  CONCLUSIONS
  Although the data support the existence of a nongenomic mechanism in mammalian skeletal muscle through which sex hormones at high concentration can rapidly modulate ClC-1, the influence of hormones on muscle excitability in vivo remains an open question.
authors.affiliation: Medical Research Council Centre for Neuromuscular Diseases, Box 102, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdom.
authors.forename: James A
authors.initials: JA
authors.lastname: Burge
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schorge
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011374:Progesterone / Q000494:pharmacology*
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; D002712:Chlorides; D011374:Progesterone; D004958:Estradiol
keywords: chloride channel; excitability; myotonia congenita; sex hormones; skeletal muscle