Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita

  • Ha, Kotdaji (Department of Physiology, Seoul National University, College of Medicine) ;
  • Kim, Sung-Young (Department of Physiology, Seoul National University, College of Medicine) ;
  • Hong, Chansik (Department of Physiology, Seoul National University, College of Medicine) ;
  • Myeong, Jongyun (Department of Physiology, Seoul National University, College of Medicine) ;
  • Shin, Jin-Hong (Department of Neurology, Research Institute for Convergence of Biomedical Research and Technology, Pusan University Yangsan Hospital) ;
  • Kim, Dae-Seong (Department of Neurology, Research Institute for Convergence of Biomedical Research and Technology, Pusan University Yangsan Hospital) ;
  • Jeon, Ju-Hong (Department of Physiology, Seoul National University, College of Medicine) ;
  • So, Insuk (Department of Physiology, Seoul National University, College of Medicine)
  • Received : 2013.09.23
  • Accepted : 2014.01.28
  • Published : 2014.03.31


ClC-1 is a member of a large family of voltage-gated chloride channels, abundantly expressed in human skeletal muscle. Mutations in ClC-1 are associated with myotonia congenita (MC) and result in loss of regulation of membrane excitability in skeletal muscle. We studied the electrophysiological characteristics of six mutants found among Korean MC patients, using patch clamp methods in HEK293 cells. Here, we found that the autosomal dominant mutants S189C and P480S displayed reduced chloride conductances compared to WT. Autosomal recessive mutant M128I did not show a typical rapid deactivation of Cl- currents. While sporadic mutant G523D displayed sustained activation of $Cl^-$ currents in the whole cell traces, the other sporadic mutants, M373L and M609K, demonstrated rapid deactivations. $V_{1/2}$ of these mutants was shifted to more depolarizing potentials. In order to identify potential effects on gating processes, slow and fast gating was analyzed for each mutant. We show that slow gating of the mutants tends to be shifted toward more positive potentials in comparison to WT. Collectively, these six mutants found among Korean patients demonstrated modifications of channel gating behaviors and reduced chloride conductances that likely contribute to the physiologic changes of MC.


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