ArticleThe Journal of clinical investigation2000
A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Substitutions of the S4DIV R2 residue (R1451) in NaScientific reports · 2018Article
- Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis.Brain : a journal of neurology · 2014Article
- Enhanced slow inactivation of the human skeletal muscle sodium channel causing normokalemic periodic paralysis.Cellular and molecular neurobiology · 2014Article
- Skeletal muscle na channel disorders.Frontiers in pharmacology · 2011Article
- Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2007Review
- An epilepsy mutation in the sodium channel SCN1A that decreases channel excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- Inherited disorders of voltage-gated sodium channels.The Journal of clinical investigation · 2005Review
- Periodic paralysis: understanding channelopathies.Current neurology and neuroscience reports · 2002Review
- Residue-specific effects on slow inactivation at V787 in D2-S6 of Na(v)1.4 sodium channels.Biophysical journal · 2001Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Hyperkalemic periodic paralysis (HyperKPP) is an autosomal dominant skeletal muscle disorder caused by single mutations in the SCN4A gene, encoding the human skeletal muscle voltage-gated Na(+) channel. We have now identified one allele with two novel mutations occurring simultaneously in the SCN4A gene. These mutations are found in two distinct families that had symptoms of periodic paralysis and malignant hyperthermia susceptibility. The two nucleotide transitions predict phenylalanine 1490-->leucine and methionine 1493-->isoleucine changes located in the transmembrane segment S5 in the fourth repeat of the alpha-subunit Na(+) channel. Surprisingly, this mutation did not affect fast inactivation parameters. The only defect produced by the double mutant (F1490L-M1493I, expressed in human embryonic kidney 293 cells) is an enhancement of slow inactivation, a unique behavior not seen in the 24 other disease-causing mutations. The behavior observed in these mutant channels demonstrates that manifestation of HyperKPP does not necessarily require disruption of slow inactivation. Our findings may also shed light on the molecular determinants and mechanism of Na(+) channel slow inactivation and help clarify the relationship between Na(+) channel defects and the long-term paralytic attacks experienced by patients with HyperKPP.
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Registered trials
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