Mutations in the cytoplasmic tail (CT) of voltage gated sodium channels cause a spectrum of inherited diseases of cellular excitability, yet to date only one mutation in the CT of the human skeletal muscle voltage gated sodium channel (hNaV1.4F1705I) has been linked to cold aggravated myotonia. The functional effects of altered regulation of hNaV1.4F1705I are incompletely understood. The locati...

used pharmaceutical agents, were investigated in excised human external intercostal muscle. The effects of anthracene-9-carboxylic acid (9-AC), a well-known myotonia-producing chemical, were also tested for comparison. In the presence of these drugs the electrical threshold was lowered, and a constant current pulse produced multiple spiking. Short trains of direct stimuli were often followed by...

Paramyotonia congenita was first described by Eulenberg (1886). It is a rare, hereditary disorder of muscle in which severe loss of power is induced by degrees of cooling which are insufficient to affect normal muscle. Myotonia also appears on cooling. However, the paralysis produced by cooling distinguishes paramyotonia from Thomsen's disease. The weakness and myotonia can easily be produced u...

Myotonia reflects a state of muscle fiber hyperexcitability. Impaired transmembrane conductance of either chloride or sodium ions results in myotonia. Myotonic disorders include the myotonic dystrophies and nondystrophic myotonias. Mutations in the genes encoding chloride (ClC-1) or sodium (SCN4A) channels expressed exclusively in skeletal muscle cause nondystrophic myotonias. Genetic defects i...