The Role of Membrane Capacitance in Cardiac Impulse Conduction: An Optogenetic Study With Non-excitable Cells Coupled to Cardiomyocytes.

Non-excitable cells (NECs) such as cardiac myofibroblasts that are electrotonically coupled to cardiomyocytes affect conduction velocity (θ) by representing a capacitive load (CL: increased membrane to be charged) and a resistive load (RL: partial depolarization of coupled cardiomyocytes). In this study, we untangled the relative contributions of both loading modalities to NEC-dependent arrhythmogenic conduction slowing. Discrimination between CL and RL was achieved by reversibly removing the RL component by light activation of the halorhodopsin-based hyperpolarizing membrane voltage actuator eNpHR3.

TGF-β (Transforming Growth Factor-β) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity.

Background: TGF-β (transforming growth factor-β) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro.

Methods And Results: Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β, applied for 24 to 48 hours at clinically relevant concentrations (≤2.

Viral gene transfer rescues arrhythmogenic phenotype and ultrastructural abnormalities in adult calsequestrin-null mice with inherited arrhythmias.

Rationale: Catecholaminergic polymorphic ventricular tachycardia is an inherited disease that predisposes to cardiac arrest and sudden death. The disease is associated with mutations in the genes encoding for the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2). CASQ2 mutations lead to a major loss of CASQ2 monomers, possibly because of enhanced degradation of the mutant protein.