International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels.
Catterall WA
et al.
Pharmacol Rev 2005 Dec;57(4)397-409
Catterall WA, Goldin AL, Waxman SG.
Pharmacol Rev 2005 Dec;57(4)397-409
Abstract: The family of voltage-gated sodium channels initiates action potentials in all types of excitable cells. Nine members of the voltage-gated sodium channel family have been characterized in mammals, and a 10th member has been recognized as a related protein. These distinct sodium channels have similar structural and functional properties, but they initiate action potentials in different cell types and have distinct regulatory and pharmacological properties. This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties.
Identification of a mutation in the gene causing hyperkalemic periodic paralysis.
Ptácek LJ
et al.
Cell 1991 Nov;67(5)1021-1027
Ptácek LJ, George AL, Griggs RC, Tawil R, Kallen RG, Barchi RL, Robertson M, Leppert MF.
Cell 1991 Nov;67(5)1021-1027
Abstract: DNA from seven unrelated patients with hyperkalemic periodic paralysis (HYPP) was examined for mutations in the adult skeletal muscle sodium channel gene (SCN4A) known to be genetically linked to the disorder. Single-strand conformation polymorphism analysis revealed aberrant bands that were unique to three of these seven patients. All three had prominent fixed muscle weakness, while the remaining four did not. Sequencing the aberrant bands demonstrated the same C to T transition in all three unrelated patients, predicting substitution of a highly conserved threonine residue with a methionine in a membrane-spanning segment of this sodium channel protein. The observation of a distinct mutation that cosegregates with HYPP in two families and appears as a de novo mutation in a third establishes SCN4A as the HYPP gene. Furthermore, this mutation is associated with a form of HYPP in which fixed muscle weakness is seen.
Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus.
Ptacek LJ
et al.
Am J Hum Genet 1991 Oct;49(4)851-854
Ptacek LJ, Trimmer JS, Agnew WS, Roberts JW, Petajan JH, Leppert M.
Am J Hum Genet 1991 Oct;49(4)851-854
Abstract: Paramyotonia congenita (PC), an autosomal dominant muscle disease, shares some clinical and electrophysiological similarities with another myotonic muscle disorder, hyperkalemic periodic paralysis (HYPP). However, clinical and electrophysiologic differences allow differentiation of the two disorders. The HYPP locus was recently shown to be linked to a skeletal muscle sodium-channel gene probe. We now report that PC maps to the same locus (LOD score 4.4, theta = 0 at assumed penetrance of .95). These linkage results, coupled with physiological data demonstrating abnormal sodium-channel function in patients with PC, implicate a sodium-channel gene as an important candidate for the site of mutation responsible for PC. Furthermore, this is strong evidence for the hypothesis that PC and HYPP are allelic disorders.
