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Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita
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 char...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society for Molecular and Cellular Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969040/ https://www.ncbi.nlm.nih.gov/pubmed/24625573 http://dx.doi.org/10.14348/molcells.2014.2267 |
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author | Ha, Kotdaji Kim, Sung-Young Hong, Chansik Myeong, Jongyun Shin, Jin-Hong Kim, Dae-Seong Jeon, Ju-Hong So, Insuk |
author_facet | Ha, Kotdaji Kim, Sung-Young Hong, Chansik Myeong, Jongyun Shin, Jin-Hong Kim, Dae-Seong Jeon, Ju-Hong So, Insuk |
author_sort | Ha, Kotdaji |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3969040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-39690402014-04-10 Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita Ha, Kotdaji Kim, Sung-Young Hong, Chansik Myeong, Jongyun Shin, Jin-Hong Kim, Dae-Seong Jeon, Ju-Hong So, Insuk Mol Cells Articles 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. Korean Society for Molecular and Cellular Biology 2014-03-31 2014-03-13 /pmc/articles/PMC3969040/ /pubmed/24625573 http://dx.doi.org/10.14348/molcells.2014.2267 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. |
spellingShingle | Articles Ha, Kotdaji Kim, Sung-Young Hong, Chansik Myeong, Jongyun Shin, Jin-Hong Kim, Dae-Seong Jeon, Ju-Hong So, Insuk Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita |
title | Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita |
title_full | Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita |
title_fullStr | Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita |
title_full_unstemmed | Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita |
title_short | Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita |
title_sort | electrophysiological characteristics of six mutations in hclc-1 of korean patients with myotonia congenita |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969040/ https://www.ncbi.nlm.nih.gov/pubmed/24625573 http://dx.doi.org/10.14348/molcells.2014.2267 |
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