ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2000
The human skeletal muscle Na channel mutation R669H associated with hypokalemic periodic paralysis enhances slow inactivation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Periodic paralysis.Handbook of clinical neurology · 2024Review
- New Challenges Resulting From the Loss of Function of NaFrontiers in pharmacology · 2021Review
- Hypokalaemic periodic paralysis with a charge-retaining substitution in the voltage sensor.Brain communications · 2020Article
- Sodium Channelopathies of Skeletal Muscle.Handbook of experimental pharmacology · 2018Review
- Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.Brain : a journal of neurology · 2016Article
- Channelopathies of skeletal muscle excitability.Comprehensive Physiology · 2015Review
- Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison.Frontiers in pharmacology · 2015Review
- Article
- Disrupted coupling of gating charge displacement to Na+ current activation for DIIS4 mutations in hypokalemic periodic paralysis.The Journal of general physiology · 2014Article
- Enhanced slow inactivation of the human skeletal muscle sodium channel causing normokalemic periodic paralysis.Cellular and molecular neurobiology · 2014Article
- Ca(V)1.1: The atypical prototypical voltage-gated Ca²⁺ channel.Biochimica et biophysica acta · 2013Review
- A calcium channel mutant mouse model of hypokalemic periodic paralysis.The Journal of clinical investigation · 2012Article
- Pathophysiological role of omega pore current in channelopathies.Frontiers in pharmacology · 2012Article
- A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis.The Journal of clinical investigation · 2011Article
- Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV.The Journal of biological chemistry · 2011Article
- Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.Neurology · 2011Article
- Skeletal muscle na channel disorders.Frontiers in pharmacology · 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Missense mutations of the human skeletal muscle voltage-gated Na channel (hSkM1) underlie a variety of diseases, including hyperkalemic periodic paralysis (HyperPP), paramyotonia congenita, and potassium-aggravated myotonia. Another disorder of sarcolemmal excitability, hypokalemic periodic paralysis (HypoPP), which is usually caused by missense mutations of the S4 voltage sensors of the L-type Ca channel, was associated recently in one family with a mutation in the outermost arginine of the IIS4 voltage sensor (R669H) of hSkM1 (Bulman et al., 1999). Intriguingly, an arginine-to-histidine mutation at the homologous position in the L-type Ca(2+) channel (R528H) is a common cause of HypoPP. We have studied the gating properties of the hSkM1-R669H mutant Na channel experimentally in human embryonic kidney cells and found that it has no significant effects on activation or fast inactivation but does cause an enhancement of slow inactivation. R669H channels exhibit an approximately 10 mV hyperpolarized shift in the voltage dependence of slow inactivation and a twofold to fivefold prolongation of recovery after prolonged depolarization. In contrast, slow inactivation is often disrupted in HyperPP-associated Na channel mutants. These results demonstrate that, in R669H-associated HypoPP, enhanced slow inactivation does not preclude, and may contribute to, prolonged attacks of weakness and add support to previous evidence implicating the IIS4 voltage sensor in slow-inactivation gating.
Indexed as
Identifiers
11102465PMC6773093W2160142455What OpenQuestion holds
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.