ClC-1 Chloride channel: Inputs on the structure–function relationship of myotonia congenita-causing mutations
Fecha
2023
Tipo
artículo original
Autores
Brenes García, Oscar Gerardo
Pusch, Michael
Morales Montero, Fernando
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Resumen
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 (CLCN1) 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 CLCN1 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.
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Palabras clave
MUTATION, ELECTROPHYSIOLOGY, MYOTONIA, CHLORIDE