Abstract
Three human genetic syndromes hyperkalemic periodic paralysis, paramyotonia congenita and potassium aggravated myotonia, have been associated in recent years with mutations of the gene SCN4A located in chromosome 17q (23.1 to 25.2) which encodes the α-subunit of the voltage-gated sodium channel of the adult skeletal muscle Barchi 1995; Cannon 1996; George 1995; Hoffman et al. 1995; Lehmann-Horn and Rüidel 1996). The 17 single-point mutations identified to date in SCN4A are spread over both cytoplasmic and extracellular regions of the polypeptide, some near the voltage sensors others near the putative inactivation domain, and do not show any obvious clustering pattern associated with distinctive clinical features. A leading pattern is missing also in the correlation of clinical syndromes and electrophysiological properties of thel0 mutations studied so far in situ (Cannon et al. 1991; Lerche et al. 1993) or in heterologous expression (Cannon and Strittmatter 1993; Hoffman et al. 1995; Ji et al. 1996; Mitrovic et al. 1995; Mitrovic et al. 1994; Mitrovic et al. 1993). The most obvious abnormalities (notably a slightly slower and incomplete inactivation) can account for muscle hyperexcitability and repetitive firing instead of normal action potentials (Cannon et al., 1993b), and are consistent with the realatively mild and episodic character of the disorders.
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Moran, O., Nizzari, M., Conti, F. (1998). Modal gating of sodium channels and possible physiological lmplications on hereditary myopathies. In: Torre, V., Nicholls, J. (eds) Neural Circuits and Networks. NATO ASI Series, vol 167. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58955-3_1
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DOI: https://doi.org/10.1007/978-3-642-58955-3_1
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