Chloride channel protein skeletal muscle (CLC-1) (CLC-1)

Chloride channel protein skeletal muscle, commonly known as CLC-1, is a voltage-gated chloride channel encoded by the CLCN1 gene and is primarily localized in the sarcolemma of skeletal muscle fibers (UniProt, P35523). It is responsible for the majority of the resting membrane conductance in these cells, which is vital for stabilizing the resting membrane potential and ensuring the rapid repolarization of the membrane after an action potential (PubMed, 30291323). By controlling the electrical excitability of the muscle, CLC-1 prevents the occurrence of spontaneous or repetitive firing that would otherwise lead to sustained muscle contraction. Mutations in the CLCN1 gene that result in a loss of function cause myotonia congenita, a genetic disorder characterized by delayed muscle relaxation and stiffness (StatPearls, NBK459217). While CLC-1 is a primary therapeutic target for treating myotonia, current pharmacological approaches often involve the use of sodium channel blockers like mexiletine to indirectly compensate for the loss of chloride conductance by reducing overall membrane excitability (PubMed, 29114044). Research continues into the development of direct CLC-1 activators as a more specific treatment strategy for myotonic disorders (NCBI, PMC5839311).

Other names

CLCN1Chloride channel 1CIC-1Skeletal muscle chloride channel

Stabilization of the skeletal muscle membrane potential by modulating chloride ion conductance to prevent repetitive firing of action potentials (PubMed, 30291323).