The gating of the CLC-1 is regulated by two processes called fast gating (protopore) and slow gating (common). Each subunit consists of highly conserved 18 transmembrane domains as well as two cystathionine beta synthase (CBS) domains in its carbonyl end. The structure of CLC-1 channel still remains unveiled, but it is confirmed that the CLC family proteins including channel and exchanger is formed by a homodimeric structure with separate pores and independent transport pathway. The CLC-1 channel belongs to a member of a large family comprising Cl − channels and Cl −/H + exchangers. Keywords: CLCN1, Clinical features, Electrophysiology, Mutation, Myotonia Congenita, Voltage gated chloride channel CLC-1 Our results provide clinical features of Korean myotonia congenita patients who have the heterozygous mutation and reveal underlying pathophyological consequences of the mutants by taking electrophysiological approach. This analysis suggests that impaired CLC-1 channel function can cause myotonia congenita and that R47W has a protective effect on A298T in relation to channel gating. However, the effect of A298T on channel gating was reduced with the presence of R47W in the same allele. The mutant channels displayed reduced chloride current density and altered channel gating. To investigate the pathological role of the mutation, electrophysiological analysis was also performed in HEK 293 cells transiently expressing homo- or heterodimeric mutant channels. The patients commonly displayed transient muscle weakness and only one patient was diagnosed with autosomal dominant type of myotonia congenita. Sequence analysis of all coding regions of the patients was performed and mutation, R47W and A298T, was commonly identified. In this study, we report 4 unrelated Korean patients diagnosed with myotonia congenita and their clinical features. CLC-1 is a voltage gated chloride channel that activates upon depolarizing potentials and play a major role in stabilization of resting membrane potentials in skeletal muscle. This disease is mainly caused by mutations of CLCN1 that encodes human skeletal muscle chloride channel (CLC-1). Myotonia congenita (MC) is a genetic disease that displays impaired relaxation of skeletal muscle and muscle hypertrophy.
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