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We report for the first time abnormalities in cardiac ventricular electrophysiology in a genetically modified murine model lacking the Scn3b gene (Scn3b(-/-)). Scn3b(-/-) mice were created by homologous recombination in embryonic stem (ES) cells. RT-PCR analysis confirmed that Scn3b mRNA was expressed in the ventricles of wild-type (WT) hearts but was(More)
The class II histone deacetylases, HDAC4 and HDAC5, directly bind to and repress myogenic transcription factors of the myocyte enhancer factor-2 (MEF-2) family thereby inhibiting skeletal myogenesis. During muscle differentiation, repression of gene transcription by MEF-2/HDAC complexes is relieved due to calcium/calmodulin-dependent (CaM) kinase-induced(More)
Activation of skeletal muscle fibers requires rapid sarcolemmal action potential (AP) conduction to ensure uniform excitation along the fiber length, as well as successful tubular excitation to initiate excitation-contraction coupling. In our companion paper in this issue, Pedersen et al. (2011. J. Gen. Physiol. doi:10.1085/jgp.201010510) quantify, for(More)
Cortical spreading depression (CSD) produces propagating waves of transient neuronal hyperexcitability followed by depression. CSD is initiated by K+ release following neuronal firing or electrical, mechanical or chemical stimuli. A triphasic (30-50 s) cortical potential transient accompanies localized transmembrane redistributions of K+, glutamate, Ca2+,(More)
BACKGROUND The SCN5A sodium channel is a major determinant for cardiac impulse propagation. We used epicardial mapping of the atria, ventricles, and septae to investigate conduction velocity (CV) in Scn5a heterozygous young and old mice. METHODS AND RESULTS Mice were divided into 4 groups: (1) young (3 to 4 months) wild-type littermates (WT); (2) young(More)
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(More)
OBJECTIVES We investigate the extent to which the electrocardiographic (ECG) properties of intact Scn5a+/- mice reproduce the corresponding clinical Brugada syndrome phenotype and use this model to investigate the role of conduction and repolarization abnormalities in the arrhythmogenic mechanism. METHODS AND RESULTS The ECGs were obtained from(More)
This paper quantifies recent experimental results through a general physical description of the mechanisms that might control two fundamental cellular parameters, resting potential (Em) and cell volume (Vc), thereby clarifying the complex relationships between them. Em was determined directly from a charge difference (CD) equation involving total(More)
Conventional microelectrode methods were used to measure variations in resting membrane potentials, E(m), of intact amphibian skeletal muscle fibres over a wide range of increased extracellular tonicities produced by inclusion of varying extracellular concentrations of sucrose. Moderate increases in extracellular tonicity to up to 2.6x normal (2.6tau) under(More)
Slowed myocardial conduction velocity (θ) is associated with an increased risk of re-entrant excitation, predisposing to cardiac arrhythmia. θ is determined by the ion channel and physical properties of cardiac myocytes and by their interconnections. Thus, θ is closely related to the maximum rate of action potential (AP) depolarization [(dV/dt)max], as(More)