ArticleHeart rhythm2014
A KCNQ1 mutation contributes to the concealed type 1 long QT phenotype by limiting the Kv7.1 channel conformational changes associated with protein kinase A phosphorylation.
Article in Heart rhythm, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 26 citations in OpenAlex.
- Not All "Idiopathic" PVCs Are Benign: Concealed Long QT Syndrome Unmasked by RVOT PVC Ablation.Journal of arrhythmia · 2026Article
- Autonomic dysregulation and atrial arrhythmias.American journal of physiology. Cell physiology · 2025Review
- Mutation-Specific Differences in Kv7.1 (International journal of molecular sciences · 2022Review
- Association of the P441L KCNQ1 variant with severity of long QT syndrome and risk of cardiac events.Frontiers in cardiovascular medicine · 2022Article
- Mutation location and IKs regulation in the arrhythmic risk of long QT syndrome type 1: the importance of the KCNQ1 S6 region.European heart journal · 2021Article
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Beta-Adrenergic Receptor Stimulation Modulates the Cellular Proarrhythmic Effects of Chloroquine and Azithromycin.Frontiers in physiology · 2020Article
- Frequency-dependent drug screening using optogenetic stimulation of human iPSC-derived cardiomyocytes.Scientific reports · 2017Article
- Quantitative analysis of the CaThe Journal of physiology · 2017Article
- The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism.Scientific reports · 2016Article
- Ion Channels in the Heart.Comprehensive Physiology · 2015Review
- Arrhythmogenic cardiomyopathy in a patient with a rare loss-of-function KCNQ1 mutation.Journal of the American Heart Association · 2015Article
- Genetics of inherited primary arrhythmia disorders.The application of clinical genetics · 2015Review
- Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy.Circulation research · 2014Review
- Phenotype guided characterization and molecular analysis of Indian patients with long QT syndromes.Indian pacing and electrophysiology journalArticle
Corrections and comments
- Commented on by
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundType 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1-encoded Kv7.1 channel that conducts the slowly activating component of the delayed rectifier K(+) current (IKs). Clinically, the diagnosis of LQT1 is complicated by variable phenotypic expressivity, whereby approximately 25% of genotype-positive individuals present with concealed LQT1 (resting corrected QT [QTc] interval ≤460 ms).
objectiveTo determine whether a specific molecular mechanism contributes to concealed LQT1.
methodsWe identified a multigenerational LQT1 family whereby 79% of the patients genotype-positive for p.Ile235Asn-KCNQ1 (I235N-Kv7.1) have concealed LQT1. We assessed the effect I235N-Kv7.1 has on IKs and the ventricular action potential (AP) by using in vitro analysis and computational simulations.
resultsClinical data showed that all 10 patients with I235N-Kv7.1 have normal resting QTc intervals but abnormal QTc interval prolongation during the recovery phase of an electrocardiographic treadmill stress test. Voltage-clamping HEK293 cells coexpressing wild-type Kv7.1 and I235N-Kv7.1 (to mimic the patients' genotypes) showed that I235N-Kv7.1 generated relatively normal functioning Kv7.1 channels but were insensitive to protein kinase A (PKA) activation. Phosphomimetic and quinidine sensitivity studies suggest that I235N-Kv7.1 limits the conformational changes in Kv7.1 channels, which are necessary to upregulate IKs after PKA phosphorylation. Computational ventricular AP simulations predicted that the PKA insensitivity of I235N-Kv7.1 is primarily responsible for prolonging the AP with β-adrenergic stimulation, especially at slower cycle lengths.
conclusionsKCNQ1 mutations that generate relatively normal Kv7.1 channels, but limit the upregulation of IKs by PKA activation, likely contribute to concealed LQT1.
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.