ArticleThe Journal of physiology1998
A defect in skeletal muscle sodium channel deactivation exacerbates hyperexcitability in human paramyotonia congenita.
Article in The Journal of physiology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans.The Journal of physiology · 1999Trial
- Changes of Resurgent NaInternational journal of molecular sciences · 2020Article
- NaScientific reports · 2018Article
- Sodium Channelopathies of Skeletal Muscle.Handbook of experimental pharmacology · 2018Review
- Differential calcium sensitivity in NaThe Journal of physiology · 2017Article
- Sodium channel biophysics, late sodium current and genetic arrhythmic syndromes.Pflugers Archiv : European journal of physiology · 2017Review
- Dynamical characterization of inactivation path in voltage-gated Na(+) ion channel by non-equilibrium response spectroscopy.Channels (Austin, Tex.) · 2016Article
- Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.Brain : a journal of neurology · 2016Article
- A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.Neurology · 2016Article
- ICEPO: the ion channel electrophysiology ontology.Database : the journal of biological databases and curation · 2016Article
- Channelopathies of skeletal muscle excitability.Comprehensive Physiology · 2015Review
- Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison.Frontiers in pharmacology · 2015Review
- A gating model for wildtype and R1448H Nav1.4 channels in paramyotonia.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2014Article
- Mechanisms of a human skeletal myotonia produced by mutation in the C-terminus of NaV1.4: is Ca2+ regulation defective?PloS one · 2013Article
- Pathophysiological role of omega pore current in channelopathies.Frontiers in pharmacology · 2012Article
- Mechanisms underlying a life-threatening skeletal muscle Na+ channel disorder.The Journal of physiology · 2011Article
- Skeletal muscle na channel disorders.Frontiers in pharmacology · 2011Article
- Biophysical costs associated with tetrodotoxin resistance in the sodium channel pore of the garter snake, Thamnophis sirtalis.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2011Article
- Ion permeation and block of the gating pore in the voltage sensor of NaV1.4 channels with hypokalemic periodic paralysis mutations.The Journal of general physiology · 2010Article
- Human voltage-gated sodium channel mutations that cause inherited neuronal and muscle channelopathies increase resurgent sodium currents.The Journal of clinical investigation · 2010Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
1. Paramyotonia congenita (PC) is a human hereditary disorder wherein missense mutations in the skeletal muscle sodium channel lead to cold-exacerbated muscle hyperexcitability. The most common site for PC mutations is the outermost arginine of domain i.v. segment 4 (human R1448, rat R1441). 2. We examined the rat homologues of two PC mutants with changes at this site: R1441P and R1441C. The R-->P mutation leads to the most clinically severe form of the disease. Since PC has so far been attributed to defects in fast inactivation, we expected the R-->P substitution to have a more dramatic effect on fast inactivation than R-->C. Both mutants (R1441P and R1441C), however, had identical rates and voltage dependence of fast inactivation and activation. 3. R1441P and R1441C also had slowed deactivation, compared with wild-type, raising the possibility that slowed deactivation, in combination with defective fast inactivation, might be a contributing cause of paramyotonia congenita. Furthermore, deactivation was slower in R1441P than in R1441C, suggesting that the worse phenotype of the human R-->P mutation is due to a greater effect on deactivation, and supporting our hypothesis that slowed sodium channel deactivation contributes to paramyotonia congenita. 4. We show that the downstroke of the muscle action potential produced a sodium tail current, and thus slowed deactivation opposes repolarization and therefore leads to hyperexcitability. Hyperexcitability due to slowed deactivation, which has previously been overlooked, also predicts the temperature sensitivity of PC, which has otherwise not been adequately explained.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.