Inhibition of tenascin C rescues abnormally reduced Na currents in dystrophin-deficient ventricular cardiomyocytes.

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a severe muscle disease caused by dystrophin deficiency. Using the mouse model for human DMD, we previously showed that the lack of dystrophin induces a significant loss of peak sodium current () in ventricular cardiomyocytes. This provided a mechanistic explanation for ventricular conduction defects and concomitant arrhythmias in the dystrophic heart.

Chronic administration of ivabradine improves cardiac Ca handling and function in a rat model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD), a severe muscle disease caused by mutations in the gene encoding for the intracellular protein dystrophin, is associated with impaired cardiac function and arrhythmias. A causative factor for complications in the dystrophic heart is abnormal calcium (Ca) handling in ventricular cardiomyocytes, and restoration of normal Ca homeostasis has emerged as therapeutic strategy. Here, we used a rodent model of DMD, the dystrophin-deficient DMD rat, to test the following hypothesis: chronic administration of ivabradine (IVA), a drug clinically approved for the treatment of heart failure, improves Ca handling in dystrophic ventricular cardiomyocytes and thereby enhances contractile performance in the dystrophic heart.

Cell size induced bias of current density in hypertrophic cardiomyocytes.

Alterations in ion channel expression and function known as "electrical remodeling" contribute to the development of hypertrophy and to the emergence of arrhythmias and sudden cardiac death. However, comparing current density values - an electrophysiological parameter commonly utilized to assess ion channel function - between normal and hypertrophied cells may be flawed when current amplitude does not scale with cell size. Even more, common routines to study equally sized cells or to discard measurements when large currents do not allow proper voltage-clamp control may introduce a selection bias and thereby confound direct comparison.

Jnk1 and downstream signalling hubs regulate anxiety-like behaviours in a zebrafish larvae phenotypic screen.

Current treatments for anxiety and depression show limited efficacy in many patients, indicating the need for further research into the underlying mechanisms. JNK1 has been shown to regulate anxiety- and depressive-like behaviours in mice, however the effectors downstream of JNK1 are not known. Here we compare the phosphoproteomes from wild-type and Jnk1-/- mouse brains and identify JNK1-regulated signalling hubs.

Empagliflozin treatment rescues abnormally reduced Na currents in ventricular cardiomyocytes from dystrophin-deficient mice.

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a severe muscle illness caused by mutations in the gene encoding for the intracellular protein dystrophin. A major source for arrhythmia vulnerability in patients with DMD is impaired ventricular impulse conduction, which predisposes for ventricular asynchrony, decreased cardiac output, and the development of reentrant circuits. Using the dystrophin-deficient mouse model for human DMD, we previously reported that the lack of dystrophin causes a significant loss of peak Na current () in ventricular cardiomyocytes.

The type of suture material affects transverse aortic constriction-induced heart failure development in mice: a repeated measures correlation analysis.

Introduction: Transverse-aortic constriction (TAC) operation is a widely used animal model to induce hypertrophy and heart failure through left-ventricular pressure overload. In mice, the cardiac response to TAC exhibits considerable variability influenced by factors such as strain, sub-strain, age, sex and vendor.

Methods: To investigate the impact of suture material (silk versus prolene) and size (6-0 versus 7-0) on the TAC-induced phenotype, we performed surgeries on male C57BL6/N mice at 9 weeks of age defining the aortic constriction by a 27G needle, thereby employing most frequently used methodological settings.

Ivabradine acutely improves cardiac Ca handling and function in a rat model of Duchenne muscular dystrophy.

The muscular dystrophies caused by dystrophin deficiency, the so-called dystrophinopathies, are associated with impaired cardiac contractility and arrhythmias, which considerably contribute to disease morbidity and mortality. Impaired Ca handling in ventricular cardiomyocytes has been identified as a causative factor for complications in the dystrophic heart, and restoration of normal Ca handling in myocytes has emerged as a promising new therapeutic strategy. In the present study, we explored the hypothesis that ivabradine, a drug clinically approved for the treatment of heart failure and stable angina pectoris, improves Ca handling in dystrophic cardiomyocytes and thereby enhances contractile performance in the dystrophic heart.

Modulation of cardiac ventricular conduction: Impact on QRS duration, amplitude and dispersion.

Alterations in cardiac impulse conduction may exert both beneficial and detrimental effects. The assessment of ventricular conduction properties is of paramount importance both in clinical and in experimental settings. Currently the duration of the QRS complex is regarded as hallmark of in-vivo assessment of global ventricular conduction time.

Evidence for a Physiological Role of T-Type Ca Channels in Ventricular Cardiomyocytes of Adult Mice.

T-type Ca channels are strongly expressed and important in the developing heart. In the adult heart, these channels play a significant role in pacemaker tissues, but there is uncertainty about their presence and physiological relevance in the working myocardium. Here, we show that the T-type Ca channel isoforms Cav3.

The Bradycardic Agent Ivabradine Acts as an Atypical Inhibitor of Voltage-Gated Sodium Channels.

Ivabradine is clinically administered to lower the heart rate, proposedly by inhibiting hyperpolarization-activated cyclic nucleotide-gated cation channels in the sinoatrial node. Recent evidence suggests that voltage-gated sodium channels (VGSC) are inhibited within the same concentration range. VGSCs are expressed within the sinoatrial node and throughout the conduction system of the heart.

Psilocybin Therapy of Psychiatric Disorders Is Not Hampered by hERG Potassium Channel-Mediated Cardiotoxicity.

Psilocybin, a hallucinogen contained in "magic" mushrooms, holds great promise for the treatment of various psychiatric disorders, and early clinical trials are encouraging. Adverse cardiac events after intake of high doses of psilocybin and a trial reporting QT interval prolongation in the electrocardiogram attributed to the drug's main metabolite, psilocin, gave rise to safety concerns. Here we show that clinical concentrations of psilocin do not cause significant human ether-a-go-go-related gene (hERG) potassium channel inhibition, a major risk factor for adverse cardiac events.

Direct measurement of protein-protein interactions by FLIM-FRET at UV laser-induced DNA damage sites in living cells.

Protein-protein interactions are essential to ensure timely and precise recruitment of chromatin remodellers and repair factors to DNA damage sites. Conventional analyses of protein-protein interactions at a population level may mask the complexity of interaction dynamics, highlighting the need for a method that enables quantification of DNA damage-dependent interactions at a single-cell level. To this end, we integrated a pulsed UV laser on a confocal fluorescence lifetime imaging (FLIM) microscope to induce localized DNA damage.

A combinatorial identity for rooted labeled forests.

In this brief note a straightforward combinatorial proof for an identity directly connecting rooted forests and unordered set partitions is provided. Furthermore, references that put this type of identity in the context of and are given.