抄録
Chloride channels had not been paid much attention by many physiologists, partly because of the lack of drastic gating. Investigations of muscle disorders with myotonia (muscle stiffness due to continued firing of action potentials), however, has conveyed numerous information about the physiology of chloride channels. The study linking chloride channel to diseases goes back to an electrophysiolgical recording from myotonic goat in 80’s, which has showed the reduction in chloride conductance, which contributes two-third of normal resting conductance. After the cloning of the chloride channel in skeletal muscle, its mutations have been identified in two forms of inheritable myotonia; autosomal dominant myotonia congenita (Thomsen) and recessive generalized myotonia (Becker). Co-expression of dominantly inherited mutant and wild type channels has suggested the dominant-negative effect of the mutant, sufficient to reduce chloride conductance drastically. The cardinal symptoms of myotonic dystrophy, the most common muscular dystrophy in adult, are muscle atrophy and myotonia. The genetic defect is abnormal expansion of CTG repeat located at 3’ untranslated region of a putative kinase gene. Electrophysiological recording from the muscle fibers of the model mice expressing expanded repeats, revealed reduced chloride conductance, attributable for myotonia. Decreased expression of channel protein due to aberrant splicing of channel mRNA has successively been shown in patients. Therefore, the myotonic dystrophy is a new form of channelopathy, caused by disrupted splicing of the ion channel mRNA. [Jpn J Physiol 55 Suppl:S8 (2005)]
