• The Korean Journal of Physiology and Pharmacology
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• 제21권4호
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• pp.439-447
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• 2017

Myotonia congenita (MC) is a genetic disease that displays impaired relaxation of skeletal muscle and muscle hypertrophy. This disease is mainly caused by mutations of CLCN1 that encodes human skeletal muscle chloride channel (CLC-1). 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. In this study, we report 4 unrelated Korean patients diagnosed with myotonia congenita and their clinical features. Sequence analysis of all coding regions of the patients was performed and mutation, R47W and A298T, was commonly identified. The patients commonly displayed transient muscle weakness and only one patient was diagnosed with autosomal dominant type of myotonia congenita. 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 mutant channels displayed reduced chloride current density and altered channel gating. However, the effect of A298T on channel gating was reduced with the presence of R47W in the same allele. 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. 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.

• Journal of Yeungnam Medical Science
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• 제16권1호
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• pp.125-130
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• 1999

저자들은 최근 25세 여자 환자로 뚜렷한 가족력이 없으면서 3-4세경부터 발생한 근육의 강직현상과 현저한 근비대소견이 있는 환자를 경험하였다. 임상적으로 타진성 근긴장증을 보이고 전기생리적 검사로 새끼손가락 외향근에서의 운동과 반복신경자극에서 복합근육활동전위의 감소를 보였으며, 이두박근의 근생검 소견상 용적이 증가된 근섬유와 중심핵화현상이 관찰되었다. 환자는 mexiletin 경구 투여후 근육의 강직현상이 다소 호전되었다. 이에 문헌고찰과 함께 Becker형 선천성 근긴장증 1례를 보고하는 바이다.

• Molecules and Cells
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• 제37권3호
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• pp.202-212
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• 2014

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.