Paced Electrogram Fractionation Analysis of Arrhythmogenic Tendency in DeltaKPQ Scn5a Mice

Head, Catherine; Balasubramaniam, Richard; Thomas, Glyn; Goddard, Catharine A.; Lei, Ming; COLLEDGE, WILLIAM H.; Grace, Andrew A.; Huang, Christopher L.‐H.

doi:10.1111/j.1540-8167.2005.50086.x

Cited by 25 publications

(74 citation statements)

References 42 publications

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“…Increased arrhythmogenicity, illustrated by spontaneous polymorphic ventricular tachycardia (VT), was also reported [35]. More recently, a similar ΔKPQ mouse line was created [36] and the results obtained were consistent with the previous study [35]. These two mouse lines allowed the investigation of anti-arrhythmic procedures and drugs.…”

Section: Scn5a Mutation δ1505-1507kpqsupporting

confidence: 67%

“…These two mouse lines allowed the investigation of anti-arrhythmic procedures and drugs. Results showed that, consistent with clinical data, β-blockers failed [36]; whereas mexiletine (Na v blocker) and rapid pacing could suppress VT [37]. It is mainly thought that the LQT-3 arrhythmogenic phenotype depends on early after-depolarisations (EAD) caused by the prolonged AP [38], however, in a recent study [39] the occurrence of so-called delayed after-depolarisations (i.e.…”

Section: Scn5a Mutation δ1505-1507kpqmentioning

confidence: 57%

“…The LQT-3 genotype, although less frequent, is often more lethal [40]. Finally, a puzzling finding of these two first studies [35,36] is that the I Na recorded from individual KI myocytes was about 2-fold larger that wild-type controls. This was not the case, however, in another recent study [39].…”

Section: Scn5a Mutation δ1505-1507kpqmentioning

confidence: 98%

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Roles and regulation of the cardiac sodium channel Nav1.5: Recent insights from experimental studies

Abriel

2007

Cardiovascular Research

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During the past decade, Na v 1.5, the main voltage-gated Na + channel in the heart, has been shown to be involved in many cardiac diseases. Genetic variants in the gene SCN5A, encoding Na v 1.5, have been linked to various cardiac phenotypes, such as the congenital and acquired long QT syndromes, Brugada syndrome, conduction slowing, sick sinus syndrome, atrial fibrillation, and even cases of dilated cardiomyopathy. This unexpected phenotypic diversity may reflect that Na v 1.5 is not only restricted to the initiation of the action potential and rapid cardiac conduction, but may also be involved in other, not-yet elucidated, functions. Despite the fact that our understanding of the regulation of expression, localization, and function of Na v 1.5 is deepening, we are still far from a comprehensive view. Much of our current knowledge has been obtained by carrying out experiments using "cellular expression systems", e.g. host cells expressing exogenous Na v 1.5. Although very informative, these techniques are limited, in that Na v 1.5 is not expressed in the physiological cellular environment of a cardiac cell. Recently, however, there have been several studies published which used approaches closer to "normal" or pathological physiology.In an attempt to summarize recently published data, this article will review the phenotypes of genetically-modified mouse strains where Na v 1.5 expression and activity are directly or indirectly modified, as well as the regulation of Na v 1.5 function using native cardiac myocytes. Despite obvious limitations, the reviewed studies provide an overview of the complex multi-factorial and multi-protein regulation of Na v 1.5.

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Section: Scn5a Mutation δ1505-1507kpqsupporting

confidence: 67%

Section: Scn5a Mutation δ1505-1507kpqmentioning

confidence: 57%

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Roles and regulation of the cardiac sodium channel Nav1.5: Recent insights from experimental studies

Abriel

2007

Cardiovascular Research

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“…в 2001 г. на экспери-ментальной модели мышей, гетерозиготных по мутации p.delKPQ1505-1507 [32,33]. Делеция расположена в непо-средственной близости от кластера из трех аминокислот (Ile-Phe-Met, IFM), которые входят в активный центр бы-строй инактивации канала [34].…”

Section: вестник рамн /2014/ № 5-6unclassified

Clinical Polymorphisms and Approaches of Arrhythmias Treatment in a Family with p.delKPQ1505-1507 Deletion in SCN5A Gene

Saber

Houshmand

Eftekhharzadeh³

et al. 2014

ARAMS

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“…In contrast, β-adrenergic stimulation suppressed arrhythmias by shortening repolarization and increasing cardiac rate, while β-blockers had no effect on their own. A second Scn5a ∆/+ mouse line, exhibiting the same phenotype as the previous line, was created (Head et al, 2005) and submitted to an extended pharmacological analysis. Electrophysiological studies performed on Langendorff-perfused whole hearts confirmed the anti-arrhythmic properties of mexiletine (Fabritz et al, 2003;Head et al, 2005) and showed that another Na + channel inhibitor, flecainide, could also prevent arrhythmias by preferentially inhibiting the late Na + current (Fredj et al, 2006), whereas β-blockers were inefficient (Head et al, 2005;Stokoe et al, 2007b; Frontiers in Physiology | Cardiac Electrophysiology Sabir et al, 2008).…”

Section: Models For the Lqt3 Syndromementioning

confidence: 99%

Mouse models of SCN5A-related cardiac arrhythmias

Charpentier

Bourgé

Mérot

2008

Progress in Biophysics and Molecular Biology

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Mutations of SCN5A gene, which encodes the α-subunit of the voltage-gated Na channel Na V 1.5, underlie hereditary cardiac arrhythmic syndromes such as the type 3 long QT syndrome, cardiac conduction diseases, the Brugada syndrome, the sick sinus syndrome, a trial standstill, and numerous overlap syndromes. Patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases. However, they could not clarify how SCN5A mutations can be responsible for such a large spectrum of diseases, for the late age of onset or the progressiveness of some of these diseases and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological mechanisms of cardiac SCN5A-related arrhythmic syndromes and several mouse models have been established. This review presents the results obtained on these models that, for most of them, recapitulate the clinical phenotypes of the patients. This includes two models knocked out for Nav1.5 β1 and β3 auxiliary subunits that are also discussed. Despite their own limitations that we point out, the mouse models still appear as powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the secondary cellular consequences of SCN5A mutations such as the expression remodeling of other genes. This points out the potential role of these genes in the overall human phenotype. Finally, they constitute useful tools for addressing the role of genetic and environmental modifiers on cardiac electrical activity.

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Paced Electrogram Fractionation Analysis of Arrhythmogenic Tendency in DeltaKPQ Scn5a Mice

Cited by 25 publications

References 42 publications

Roles and regulation of the cardiac sodium channel Nav1.5: Recent insights from experimental studies

Roles and regulation of the cardiac sodium channel Nav1.5: Recent insights from experimental studies

Clinical Polymorphisms and Approaches of Arrhythmias Treatment in a Family with p.delKPQ1505-1507 Deletion in SCN5A Gene

Mouse models of SCN5A-related cardiac arrhythmias

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