ArticleThe Journal of physiology2006
Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique.
Article in The Journal of physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Biophysical mechanisms of myocardium sodium channelopathies.Pflugers Archiv : European journal of physiology · 2024Review
- The Dynamic Clamp Technique: A Robust Toolkit for Investigating Potassium Channel Function.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Mexiletine Treatment for Neonatal LQT3 Syndrome: Case Report and Literature Review.Frontiers in pediatrics · 2021Article
- Dynamic action potential clamp predicts functional separation in mild familial and severe de novo forms ofProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Dysfunctional Nav1.5 channels due to SCN5A mutations.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.The Journal of physiology · 2017Article
- Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing.Frontiers in physiology · 2017Review
- Mutational analysis of SCN5A gene in long QT syndrome.Meta gene · 2015Article
- The late Na+ current--origin and pathophysiological relevance.Cardiovascular drugs and therapy · 2013Review
- Regulation of intracellular Na(+) in health and disease: pathophysiological mechanisms and implications for treatment.Global cardiology science & practice · 2013Review
- Cardiac ion channelopathies and the sudden infant death syndrome.ISRN cardiology · 2012Article
- Rapid genetic algorithm optimization of a mouse computational model: benefits for anthropomorphization of neonatal mouse cardiomyocytes.Frontiers in physiology · 2012Article
- Shaping a new Ca²⁺ conductance to suppress early afterdepolarizations in cardiac myocytes.The Journal of physiology · 2011Article
- The effect of ranolazine on the vasodilator-induced myocardial perfusion abnormality.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2011Article
- Article
- Anthropomorphizing the mouse cardiac action potential via a novel dynamic clamp method.Biophysical journal · 2009Article
- Re-evaluating the efficacy of beta-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling.Cardiovascular research · 2009Article
- Contribution of long-QT syndrome genetic variants in sudden infant death syndrome.Pediatric cardiology · 2009Article
- The cardiac persistent sodium current: an appealing therapeutic target?British journal of pharmacology · 2008Review
- Dynamic clamp: a powerful tool in cardiac electrophysiology.The Journal of physiology · 2006Review
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6 authors.
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Abstract
Long-QT3 syndrome (LQT3) is linked to cardiac sodium channel gene (SCN5A) mutations. In this study, we used the 'dynamic action potential clamp' (dAPC) technique to effectively replace the native sodium current (I(Na)) of the Priebe-Beuckelmann human ventricular cell model with wild-type (WT) or mutant I(Na) generated in a human embryonic kidney (HEK)-293 cell that is voltage clamped by the free-running action potential of the ventricular cell. We recorded I(Na) from HEK cells expressing either WT or LQT3-associated Y1795C or A1330P SCN5A at 35 degrees C, and let this current generate and shape the action potential (AP) of subepicardial, mid-myocardial and subendocardial model cells. The HEK cell's endogenous background current was completely removed by a real-time digital subtraction procedure. With WT I(Na), AP duration (APD) was longer than with the original Priebe-Beuckelmann model I(Na), due to a late I(Na) component of approximately 30 pA that could not be revealed with conventional voltage-clamp protocols. With mutant I(Na), this late component was larger ( approximately 100 pA), producing a marked increase in APD ( approximately 70-80 ms at 1 Hz for the subepicardial model cell). The late I(Na) magnitude showed reverse frequency dependence, resulting in a significantly steeper APD-frequency relation in the mutant case. AP prolongation was more pronounced for the mid-myocardial cell type, resulting in increased APD dispersion for each of the mutants. For both mutants, a 2 s pause following rapid (2 Hz) pacing resulted in distorted AP morphology and beat-to-beat fluctuations of I(Na). Our dAPC data directly demonstrate the arrhythmogenic nature of LQT3-associated SCN5A mutations.
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