title: Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.
abstract: BACKGROUND
  Hypokalemic periodic paralysis (HypoPP) is associated with mutations in either the Ca(V)1.1 calcium channel or the Na(V)1.4 sodium channel. Some Na(V)1.4 HypoPP mutations have been shown to cause an anomalous inward current that may contribute to the attacks of paralysis. Herein, we test whether disease-associated Na(V)1.4 mutations in previously untested homologous regions of the channel also give rise to the anomalous current.
  
  
  METHODS
  The functional properties of mutant Na(V)1.4 channels were studied with voltage-clamp techniques in an oocyte expression system.
  
  
  RESULTS
  The HypoPP mutation Na(V)1.4-R1132Q conducts an anomalous gating pore current, but the homologous R1448C mutation in paramyotonia congenita does not.
  
  
  CONCLUSIONS
  Gating pore currents arising from missense mutations at arginine residues in the voltage sensor domains of Na(V)1.4 are a common feature of HypoPP mutant channels and contribute to the attacks of paralysis.
authors.affiliation: Department of Anesthesiology, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Francis
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Rybalchenko
authors.forename: Arie
authors.initials: A
authors.lastname: Struyk
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cannon
mesh_terms: D000818:Animals; D001120:Arginine / Q000235:genetics; D002118:Calcium / Q000494:pharmacology; D003545:Cysteine / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005973:Glutamine / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics*; D008845:Microinjections / Q000379:methods; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020967:Myotonic Disorders / Q000235:genetics; D062553:NAV1.4 Voltage-Gated Sodium Channel; D009865:Oocytes; D020513:Paralysis, Hyperkalemic Periodic / Q000235:genetics; D018408:Patch-Clamp Techniques; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D009124:Muscle Proteins; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D005973:Glutamine; D013779:Tetrodotoxin; D001120:Arginine; D003545:Cysteine; D002118:Calcium