ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations
Myotonia congenita is a hereditary muscle disease mainly characterized by muscle hyperexcitability, which leads to a sustained burst of discharges that correlates with the magnitude and duration of involuntary aftercontractions, muscle stiffness, and hypertrophy. Mutations in the chloride voltage-ga...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/10/2622 |
| _version_ | 1797574674731761664 |
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| author | Oscar Brenes Michael Pusch Fernando Morales |
| author_facet | Oscar Brenes Michael Pusch Fernando Morales |
| author_sort | Oscar Brenes |
| collection | DOAJ |
| description | Myotonia congenita is a hereditary muscle disease mainly characterized by muscle hyperexcitability, which leads to a sustained burst of discharges that correlates with the magnitude and duration of involuntary aftercontractions, muscle stiffness, and hypertrophy. Mutations in the chloride voltage-gated channel 1 (<i>CLCN1</i>) gene that encodes the skeletal muscle chloride channel (ClC-1) are responsible for this disease, which is commonly known as myotonic chloride channelopathy. The biophysical properties of the mutated channel have been explored and analyzed through in vitro approaches, providing important clues to the general function/dysfunction of the wild-type and mutated channels. After an exhaustive search for <i>CLCN1</i> mutations, we report in this review more than 350 different mutations identified in the literature. We start discussing the physiological role of the ClC-1 channel in skeletal muscle functioning. Then, using the reported functional effects of the naturally occurring mutations, we describe the biophysical and structural characteristics of the ClC-1 channel to update the knowledge of the function of each of the ClC-1 helices, and finally, we attempt to point out some patterns regarding the effects of mutations in the different helices and loops of the protein. |
| first_indexed | 2024-03-10T21:25:40Z |
| format | Article |
| id | doaj.art-9eacec5052474ff3a1cb910e3563e020 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T21:25:40Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-9eacec5052474ff3a1cb910e3563e0202023-11-19T15:44:41ZengMDPI AGBiomedicines2227-90592023-09-011110262210.3390/biomedicines11102622ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing MutationsOscar Brenes0Michael Pusch1Fernando Morales2Departamento de Fisiología, Escuela de Medicina, Universidad de Costa Rica, San José 11501-2060, Costa RicaIstituto di Biofisica, Consiglio Nazionale delle Ricerche (CNR), Via De Marini 6, 16149 Genova, ItalyInstituto de Investigaciones en Salud (INISA), Universidad de Costa Rica, San José 11501-2060, Costa RicaMyotonia congenita is a hereditary muscle disease mainly characterized by muscle hyperexcitability, which leads to a sustained burst of discharges that correlates with the magnitude and duration of involuntary aftercontractions, muscle stiffness, and hypertrophy. Mutations in the chloride voltage-gated channel 1 (<i>CLCN1</i>) gene that encodes the skeletal muscle chloride channel (ClC-1) are responsible for this disease, which is commonly known as myotonic chloride channelopathy. The biophysical properties of the mutated channel have been explored and analyzed through in vitro approaches, providing important clues to the general function/dysfunction of the wild-type and mutated channels. After an exhaustive search for <i>CLCN1</i> mutations, we report in this review more than 350 different mutations identified in the literature. We start discussing the physiological role of the ClC-1 channel in skeletal muscle functioning. Then, using the reported functional effects of the naturally occurring mutations, we describe the biophysical and structural characteristics of the ClC-1 channel to update the knowledge of the function of each of the ClC-1 helices, and finally, we attempt to point out some patterns regarding the effects of mutations in the different helices and loops of the protein.https://www.mdpi.com/2227-9059/11/10/2622myotoniachloride channelelectrophysiologychannelopathymutation |
| spellingShingle | Oscar Brenes Michael Pusch Fernando Morales ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations Biomedicines myotonia chloride channel electrophysiology channelopathy mutation |
| title | ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations |
| title_full | ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations |
| title_fullStr | ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations |
| title_full_unstemmed | ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations |
| title_short | ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations |
| title_sort | clc 1 chloride channel inputs on the structure function relationship of myotonia congenita causing mutations |
| topic | myotonia chloride channel electrophysiology channelopathy mutation |
| url | https://www.mdpi.com/2227-9059/11/10/2622 |
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