ArticlePloS one2011
Alternative splicing of the cardiac sodium channel creates multiple variants of mutant T1620K channels.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Cardiac Involvement in Myotonic Dystrophy Type 1: Mechanisms, Clinical Perspectives, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Blocking the voltage-gated sodium channel hNaFEBS open bio · 2025Article
- Block of Voltage-Gated Sodium Channels by Aripiprazole in a State-Dependent Manner.International journal of molecular sciences · 2022Article
- Coupling the Cardiac Voltage-Gated Sodium Channel to Channelrhodopsin-2 Generates Novel Optical Switches for Action Potential Studies.Membranes · 2022Article
- Article
- Block of Voltage-Gated Sodium Channels by Atomoxetine in a State- and Use-dependent Manner.Frontiers in pharmacology · 2021Article
- Block of Voltage-Gated Sodium Channels as a Potential Novel Anti-cancer Mechanism of TIC10.Frontiers in pharmacology · 2021Article
- Action potentials in Xenopus oocytes triggered by blue light.The Journal of general physiology · 2020Article
- Biophysical mechanisms for QRS- and QTc-interval prolongation in mice with cardiac expression of expanded CUG-repeat RNA.The Journal of general physiology · 2020Article
- Life Cycle of the Cardiac Voltage-Gated Sodium Channel NaFrontiers in physiology · 2020Review
- Dysfunctional Nav1.5 channels due to SCN5A mutations.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Molecular expression of multiple Nav1.5 splice variants in the frontal lobe of the human brain.International journal of molecular medicine · 2018Article
- Multiple Nav1.5 isoforms are functionally expressed in the brain and present distinct expression patterns compared with cardiac Nav1.5.Molecular medicine reports · 2017Article
- State-dependent block of voltage-gated sodium channels by the casein-kinase 1 inhibitor IC261.Investigational new drugs · 2017Article
- Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.Nature communications · 2016Article
- Reduced Penetrance and Variable Expression of SCN5A Mutations and the Importance of Co-inherited Genetic Variants: Case Report and Review of the Literature.Indian pacing and electrophysiology journal · 2014Article
- Exon 11 skipping of SCN10A coding for voltage-gated sodium channels in dorsal root ganglia.Channels (Austin, Tex.) · 2014Article
- Characterization of N-terminally mutated cardiac Na(+) channels associated with long QT syndrome 3 and Brugada syndrome.Frontiers in physiology · 2013Article
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative splicing creates several Na(v)1.5 transcripts in the mammalian myocardium and in various other tissues including brain, dorsal root ganglia, breast cancer cells as well as neuronal stem cell lines. In total nine Na(v)1.5 splice variants have been discovered. Four of them, namely Na(v)1.5a, Na(v)1.5c, Na(v)1.5d, and Na(v)1.5e, generate functional channels in heterologous expression systems. The significance of alternatively spliced transcripts for cardiac excitation, in particular their role in SCN5A channelopathies, is less well understood. In the present study, we systematically investigated electrophysiological properties of mutant T1620K channels in the background of all known functional Na(v)1.5 splice variants in HEK293 cells. This mutation has been previously associated with two distinct cardiac excitation disorders: with long QT syndrome type 3 (LQT3) and isolated cardiac conduction disease (CCD). When investigating the effect of the T1620K mutation, we noticed similar channel defects in the background of hNa(v)1.5, hNa(v)1.5a, and hNa(v)1.5c. In contrast, the hNa(v)1.5d background produced differential effects: In the mutant channel, some gain-of-function features did not emerge, whereas loss-of-function became more pronounced. In case of hNa(v)1.5e, the neonatal variant of hNa(v)1.5, both the splice variant itself as well as the corresponding mutant channel showed electrophysiological properties that were distinct from the wild-type and mutant reference channels, hNa(v)1.5 and T1620K, respectively. In conclusion, our data show that alternative splicing is a mechanism capable of generating a variety of functionally distinct wild-type and mutant hNa(v)1.5 channels. Thus, the cellular splicing machinery is a potential player affecting genotype-phenotype correlations in SCN5A channelopathies.
Indexed as
Identifiers
What 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.