ArticleThe Journal of physiology2007
Effects of L-type Ca2+ channel antagonism on ventricular arrhythmogenesis in murine hearts containing a modification in the Scn5a gene modelling human long QT syndrome 3.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Defining Cardiomyocyte Repolarization Response to Pharmacotherapy in Long-QT Syndrome Type 3.Journal of the American Heart Association · 2024Article
- NGCN: Drug-target interaction prediction by integrating information and feature learning from heterogeneous network.Journal of cellular and molecular medicine · 2024Article
- NaScientific reports · 2021Article
- Genetic Loss ofCirculation. Arrhythmia and electrophysiology · 2020Article
- Experimental analysis of the onset mechanism of TdP reported in an LQT3 patient during pharmacological treatment with serotonin-dopamine antagonists against insomnia and nocturnal delirium.Heart and vessels · 2020Article
- Ion channels, long QT syndrome and arrhythmogenesis in ageing.Clinical and experimental pharmacology & physiology · 2017Review
- Pro-arrhythmic atrial phenotypes in incrementally paced murine Pgc1βExperimental physiology · 2017Article
- The effects of ageing and adrenergic challenge on electrocardiographic phenotypes in a murine model of long QT syndrome type 3.Scientific reports · 2017Article
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
- Modulation of the QT interval duration in hypertension with antihypertensive treatment.Hypertension research : official journal of the Japanese Society of Hypertension · 2015Review
- Nonequilibrium reactivation of Na+ current drives early afterdepolarizations in mouse ventricle.Circulation. Arrhythmia and electrophysiology · 2014Article
- Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia.Stem cell reports · 2014Article
- Development of a swine model of left bundle branch block for experimental studies of cardiac resynchronization therapy.Journal of cardiovascular translational research · 2013Article
- Fendiline inhibits K-Ras plasma membrane localization and blocks K-Ras signal transmission.Molecular and cellular biology · 2013Article
- Effects of calmodulin-dependent protein kinase II inhibitor, KN-93, on electrophysiological features of rabbit hypertrophic cardiac myocytes.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2012Article
- Pathophysiology of the cardiac late Na current and its potential as a drug target.Journal of molecular and cellular cardiology · 2012Review
- Mouse Models of SCN5A-Related Cardiac Arrhythmias.Frontiers in physiology · 2012Article
- Autonomic modulation and antiarrhythmic therapy in a model of long QT syndrome type 3.Cardiovascular research · 2010Article
- Acute atrial arrhythmogenesis in murine hearts following enhanced extracellular Ca(2+) entry depends on intracellular Ca(2+) stores.Acta physiologica (Oxford, England) · 2010Article
- Roscovitine binds to novel L-channel (CaV1.2) sites that separately affect activation and inactivation.The Journal of biological chemistry · 2010Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Ventricular arrhythmogenesis in long QT 3 syndrome (LQT3) involves both triggered activity and re-entrant excitation arising from delayed ventricular repolarization. Effects of specific L-type Ca2+ channel antagonism were explored in a gain-of-function murine LQT3 model produced by a DeltaKPQ 1505-1507 deletion in the SCN5A gene. Monophasic action potentials (MAPs) were recorded from epicardial and endocardial surfaces of intact, Langendorff-perfused Scn5a+/Delta hearts. In untreated Scn5a+/Delta hearts, epicardial action potential duration at 90% repolarization (APD90) was 60.0 +/- 0.9 ms compared with 46.9 +/- 1.6 ms in untreated wild-type (WT) hearts (P < 0.05; n = 5). The corresponding endocardial APD(90) values were 52.0 +/- 0.7 ms and 53.7 +/- 1.6 ms in Scn5a+/Delta and WT hearts, respectively (P > 0.05; n = 5). Epicardial early afterdepolarizations (EADs), often accompanied by spontaneous ventricular tachycardia (VT), occurred in 100% of MAPs from Scn5a+/Delta but not in any WT hearts (n = 10). However, EAD occurrence was reduced to 62 +/- 7.1%, 44 +/- 9.7%, 10 +/- 10% and 0% of MAPs following perfusion with 10 nm, 100 nm, 300 nm and 1 mum nifedipine, respectively (P < 0.05; n = 5), giving an effective IC50 concentration of 79.3 nm. Programmed electrical stimulation (PES) induced VT in all five Scn5a+/Delta hearts (n = 5) but not in any WT hearts (n = 5). However, repeat PES induced VT in 3, 2, 2 and 0 out of 5 Scn5a+/Delta hearts following perfusion with 10 nm, 100 nm, 300 nm and 1 mum nifedipine, respectively. Patch clamp studies in isolated ventricular myocytes from Scn5a+/Delta and WT hearts confirmed that nifedipine (300 nm) completely suppressed the inward Ca2+ current but had no effect on inward Na+ currents. No significant effects were seen on epicardial APD90, endocardial APD90 or ventricular effective refractory period in Scn5a+/Delta and WT hearts following perfusion with nifedipine at 1 nm, 10 nm, 100 nm, 300 nm and 1 microm nifedipine concentrations. We conclude that L-type Ca2+ channel antagonism thus exerts specific anti-arrhythmic effects in Scn5a+/Delta hearts through suppression of EADs.
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