ArticleThe Journal of physiology2005
A C-terminal skeletal muscle sodium channel mutation associated with myotonia disrupts fast inactivation.
Article in The Journal of physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- Article
- Feedback contributions to excitation-contraction coupling in native functioning striated muscle.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Gene panel analysis of 119 index patients with suspected periodic paralysis in Japan.Frontiers in neurology · 2023Article
- Ca2+-dependent modulation of voltage-gated myocyte sodium channels.Biochemical Society transactions · 2021Review
- Structural basis of cytoplasmic NaV1.5 and NaV1.4 regulation.The Journal of general physiology · 2021Review
- Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.Lancet (London, England) · 2018Article
- Sodium Channelopathies of Skeletal Muscle.Handbook of experimental pharmacology · 2018Review
- Calmodulin and Ca(2+) control of voltage gated Na(+) channels.Channels (Austin, Tex.) · 2016Review
- A rendezvous with the queen of ion channels: Three decades of ion channel research by David T Yue and his Calcium Signals Laboratory.Channels (Austin, Tex.) · 2016Article
- Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome.Annals of neurology · 2015Article
- Channelopathies of skeletal muscle excitability.Comprehensive Physiology · 2015Review
- Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage-Gated Calcium and Sodium Channels.Current molecular pharmacology · 2015Review
- Article
- An algorithm for candidate sequencing in non-dystrophic skeletal muscle channelopathies.Journal of neurology · 2013Article
- Mechanisms of a human skeletal myotonia produced by mutation in the C-terminus of NaV1.4: is Ca2+ regulation defective?PloS one · 2013Article
- Voltage-gated sodium channel-associated proteins and alternative mechanisms of inactivation and block.Cellular and molecular life sciences : CMLS · 2012Review
- The Na conductance in the sarcolemma and the transverse tubular system membranes of mammalian skeletal muscle fibers.The Journal of general physiology · 2011Article
- Mechanisms underlying a life-threatening skeletal muscle Na+ channel disorder.The Journal of physiology · 2011Article
- Gating behaviour of sodium currents in adult mouse muscle recorded with an improved two-electrode voltage clamp.The Journal of physiology · 2011Article
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Authors and funding
4 authors.
Funding
Abstract
Missense mutations in the skeletal muscle sodium channel alpha-subunit gene (SCN4A) are associated with a group of clinically overlapping diseases caused by alterations in the excitability of the sarcolemma. Sodium channel defects may increase excitability and cause myotonic stiffness or may render fibres transiently inexcitable to produce periodic paralysis. A patient with cold-aggravated myotonia did not harbour any of the common SCN4A mutations. We therefore screened all 24 exons by denaturing high-performance liquid chromatography, followed by direct sequencing. Two novel missense changes were found with predicted amino acid substitutions: T323M in the DIS5-S6 loop and F1705I in the intracellular C-terminus. The functional impact of these substitutions was assessed by recording whole-cell Na+ currents from transiently transfected HEK293 cells. T323M currents were indistinguishable from wild-type (WT). Fast inactivation was impaired for F1705I channels, as demonstrated by an 8.6-mV rightwards shift in voltage dependence and a two-fold slowing in the rate of inactivation. Recovery from fast inactivation was not altered, nor was there an increase in the persistent current after a 50- ms depolarization. Activation and slow inactivation were not appreciably affected. These data suggest that T323M is a benign polymorphism, whereas F1705I results in fast inactivation defects, which are often observed for myotonia. This is the first example of a C-terminal mutation in SCN4A associated with human disease. Like the cardiac disorders (long QT syndrome type 3 or Brugada syndrome) and generalized epilepsy with febrile seizures plus (GEFS+) associated with C-terminal mutations in other NaV channels, the primary effect of F1705I was a partial disruption of fast inactivation.
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