Introduction of CLCN1
Chloride channel protein (CLCN1), also known as skeletal muscle, is a protein that is encoded by the CLCN1 gene. Mutations in this protein can bring about congenital myotonia. There are several methods to regulate this channel. Activation of the fast and slow gating of CLCN1 requires depolarization, which is dependent on the Cl- and H+ concentration. Adenosine nucleotides’ inhibition of CLCN1 can be regulated by oxidation and reduction. ATP inhibition only reduces CLCN1 channels by shifting the voltage-dependence of common gating to more positive condition. PKC and Zn2+ are also found to modulate CLCN1 function. Skeletal muscle has a uniquely high resting Cl- conductance, which is more than four times greater than the K+ conductance.
|Basic Information of CLCN1|
|Protein Name||Chloride channel protein 1|
|Aliases||skeletal muscle, ClC-1|
|Organism||Homo sapiens (Human)|
Function of CLCN1 Membrane Protein
CLCN1 plays an important role in human’s body. CLCN1 is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contraction and relaxation are controlled by the flow of ions into and out of muscle cells. CLCN1 forms an ion channel that controls the flow of negatively charged chloride ions into these cells. The main function of this channel is to stabilize the cells' electrical charge, enabling muscles to contract normally. CLCN1 is the predominant mediator of the Cl- conductance in skeletal muscle and regulates the happen of myotonia congenita. Using the crystal structure of cmClC (a eukaryotic ClC exchanger) as a model for human ClC-1 allows the identification of residues found mutated in myotonic patients in the dimer interface and in the ion conduction protopore. To surpass ClC-1 defect, the ideal drug should specifically enhance its Cl- currents; unfortunately, this objective seems to be far from completion.
Fig1. ClC-1 is a major ion channel involved in the membrane resting potential of skeletal muscles. (Poroca, 2017)
Application of CLCN1 Membrane Protein in Literature
This article records recent experiments using a combination of cellular electrophysiology, molecular genetics, and recombinant DNA technology to study the molecular basis of ion permeation and selection in ClC-type chloride channels.
The article suggests that the properties of disease caused by mutations may be helpful in explaining the functional properties of the CLC-1 channel, which has been a part of a nine-member gene family of chloride channels. The large amount of knowledge obtained for CLC-1 may also help a better understanding of the other CLC channels, three of which also participate in genetic diseases.
This article suggests that mutations in the skeletal muscle chloride channel gene CLCN1 on chromosome 7 can cause myotonia congenita, which is a hereditary chloride channel disorder characterized by delayed relaxation of skeletal muscle (myotonia). The author also summarizes existing knowledge about phenotypic variability and discusses the possible contributing factors.
This article suggests that alternative splicing influences the expression and function of the skeletal muscle chloride channel CLCN1/ClC-1. Inclusion of the CLCN1 exon 7A is aberrantly elevated in myotonic dystrophy (DM), which is a genetic disordered disease caused by the expansion of a CTG or CCTG repeat. Collectively, all their results show a mechanistic model to regulate the activity of Clcn1 splicing and discover novel regulatory properties of MBNL and CELF proteins.
As non-dystrophic myotonias (NDMs) are caused by mutations in CLCN1 or SCN4A, this article aims to find out the best genetic characterization of NDM in the Netherlands by analyzing CLCN1 and SCN4A in tandem. The current results show that families with NDM afford high-level mutation ascertainment in tandem analysis of CLCN1 and SCN4A.
CLCN1 Preparation Options
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