ArticleProceedings of the National Academy of Sciences of the United States of America2008
Depolarization-activated gating pore current conducted by mutant sodium channels in potassium-sensitive normokalemic periodic paralysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 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
- Article
- Voltage sensors.Molecular pharmacology · 2025Review
- Pathogenic gating pore current conducted by autism-related mutations in the NaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology.Channels (Austin, Tex.) · 2023Review
- Maturation of iPSC-derived cardiomyocytes in a heart-on-a-chip device enables modeling of dilated cardiomyopathy caused by R222Q-SCN5A mutation.Biomaterials · 2023Article
- Fifty years of gating currents and channel gating.The Journal of general physiology · 2023Review
- Optical measurement of gating pore currents in hypokalemic periodic paralysis model cells.Disease models & mechanisms · 2023Article
- CaHandbook of experimental pharmacology · 2023Article
- The voltage-sensing domain of a hERG1 mutant is a cation-selective channel.Biophysical journal · 2022Article
- Structural and Functional Characterization of a Novel Scorpion Toxin that Inhibits NaFrontiers in pharmacology · 2022Article
- Autism-associated mutations in KProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
- Proton Quantum Tunneling: Influence and Relevance to Acidosis-Induced Cardiac Arrhythmias/Cardiac Arrest.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Article
- Voltage-Gated CaFrontiers in synaptic neuroscience · 2021Review
- New Challenges Resulting From the Loss of Function of NaFrontiers in pharmacology · 2021Review
- Skeletal muscle CaPflugers Archiv : European journal of physiology · 2020Review
- Structure of the Cardiac Sodium Channel.Cell · 2020Article
- Noncanonical Ion Channel Behaviour in Pain.International journal of molecular sciences · 2019Review
- Cell-Free Expression of Sodium Channel Domains for Pharmacology Studies. Noncanonical Spider Toxin Binding Site in the Second Voltage-Sensing Domain of Human NaFrontiers in pharmacology · 2019Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Some inherited periodic paralyses are caused by mutations in skeletal muscle Na(V)1.4 sodium channels that alter channel gating and impair action potential generation. In the case of hypokalemic periodic paralysis, mutations of one of the outermost two gating charges in the S4 voltage sensor in domain II of the Na(V)1.4 alpha subunit induce gating pore current, resulting in a leak of sodium or protons through the voltage sensor that causes depolarization, sodium overload, and contractile failure correlated with low serum potassium. Potassium-sensitive normokalemic periodic paralysis (NormoPP) is caused by mutations in the third gating charge in domain II of the Na(V)1.4 channel. Here, we report that these mutations in rat Na(V)1.4 (R669Q/G/W) cause gating pore current that is activated by depolarization and therefore is conducted in the activated state of the voltage sensor. In addition, we find that this gating pore current is retained in the slow-inactivated state and is deactivated only at hyperpolarized membrane potentials. Gating pore current through the mutant voltage sensor of slow-inactivated NormoPP channels would cause increased sodium influx at the resting membrane potential and during trains of action potentials, depolarize muscle fibers, and lead to contractile failure and cellular pathology in NormoPP.
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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.