ArticleJournal of molecular and cellular cardiology2009
Diastolic transient inward current in long QT syndrome type 3 is caused by Ca2+ overload and inhibited by ranolazine.
Article in Journal of molecular and cellular cardiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01728025 (Long Term Prophylactic Therapy of Congenital Long QT Syndrome Type III), which is not on this map. Cited by 24 papers.
What it found
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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.
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.
Long Term Prophylactic Therapy of Congenital Long QT Syndrome Type III (LQT3) With Ranolazine
Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Ranolazine for Congenital Long-QT Syndrome Type III: Experimental and Long-Term Clinical Data.Circulation. Arrhythmia and electrophysiology · 2016Trial
- Long QT syndrome type 3 gain-of-function of NaCommunications biology · 2025Article
- Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside.Circulation research · 2024Review
- Review
- Activation of small conductance CaThe Journal of physiology · 2023Article
- Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus.International journal of molecular sciences · 2022Review
- Late sodium current and calcium homeostasis in arrhythmogenesis.Channels (Austin, Tex.) · 2021Review
- A novel substrate for arrhythmias in Chagas disease.PLoS neglected tropical diseases · 2021Article
- Cardiac Late Sodium Channel Current Is a Molecular Target for the Sodium/Glucose Cotransporter 2 Inhibitor Empagliflozin.Circulation · 2021Article
- Heritable arrhythmia syndromes associated with abnormal cardiac sodium channel function: ionic and non-ionic mechanisms.Cardiovascular research · 2020Review
- Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.Frontiers in pharmacology · 2020Review
- Ion channels, long QT syndrome and arrhythmogenesis in ageing.Clinical and experimental pharmacology & physiology · 2017Review
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
- Molecular Pathophysiology of Congenital Long QT Syndrome.Physiological reviews · 2017Review
- Ranolazine is an Effective and Safe Treatment of Adults with Symptomatic Premature Ventricular Contractions due to Triggered Ectopy.The International journal of angiology : official publication of the International College of Angiology, Inc · 2016Article
- Ranolazine for the suppression of ventricular arrhythmia: a case series.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2014Article
- Cardiac sodium channelopathy associated with SCN5A mutations: electrophysiological, molecular and genetic aspects.The Journal of physiology · 2013Review
- Antiarrhythmic effects of the highly selective late sodium channel current blocker GS-458967.Heart rhythm · 2013Article
- X-ROS signaling in the heart and skeletal muscle: stretch-dependent local ROS regulates [Ca²⁺]i.Journal of molecular and cellular cardiology · 2013Review
- 18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels.Acta pharmacologica Sinica · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Long QT syndrome variant 3 (LQT-3) is a channelopathy in which mutations in SCN5A, the gene coding for the primary heart Na(+) channel alpha subunit, disrupt inactivation to elevate the risk of mutation carriers for arrhythmias that are thought to be calcium (Ca(2+))-dependent. Spontaneous arrhythmogenic diastolic activity has been reported in myocytes isolated from mice harboring the well-characterized Delta KPQ LQT-3 mutation but the link to altered Ca(2+) cycling related to mutant Na(+) channel activity has not previously been demonstrated. Here we have investigated the relationship between elevated sarcoplasmic reticulum (SR) Ca(2+) load and induction of spontaneous diastolic inward current (I(TI)) in myocytes expressing Delta KPQ Na(+) channels, and tested the sensitivity of both to the antianginal compound ranolazine. We combined whole-cell patch clamp measurements, imaging of intracellular Ca(2+), and measurement of SR Ca(2+) content using a caffeine dump methodology. We compared the Ca(2+) content of Delta KPQ(+/-) myocytes displaying I(TI) to those without spontaneous diastolic activity and found that I(TI) induction correlates with higher sarcoplasmic reticulum (SR) Ca(2+). Both spontaneous diastolic I(TI) and underlying Ca(2+) waves are inhibited by ranolazine at concentrations that preferentially target I(NaL) during prolonged depolarization. Furthermore, ranolazine I(TI) inhibition is accompanied by a small but significant decrease in SR Ca(2+) content. Our results provide the first direct evidence that induction of diastolic transient inward current (I(TI)) in Delta KPQ(+/-) myocytes occurs under conditions of elevated SR Ca(2+) load.
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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.