Determinants of electrical propagation and propagation block in Arrhythmogenic Cardiomyopathy.

Gap junction and ion channel remodeling occur early in Arrhythmogenic Cardiomyopathy (ACM), but their pathogenic consequences have not been elucidated. Here, we identified the arrhythmogenic substrate, consisting of propagation slowing and conduction block, in ACM models expressing two different desmosomal gene variants. Neonatal rat ventricular myocytes were transduced to express variants in genes encoding desmosomal proteins plakoglobin or plakophilin-2.

A detailed analysis of single-channel Na 1.5 recordings does not reveal any cooperative gating.

Cardiac voltage-gated sodium (Na ) channels (Na 1.5) are crucial for myocardial electrical excitation. Recent studies based on single-channel recordings have suggested that Na channels interact functionally and exhibit coupled gating.

Modeling the Interactions Between Sodium Channels Provides Insight Into the Negative Dominance of Certain Channel Mutations.

Background: Na1.5 cardiac Na channel mutations can cause arrhythmogenic syndromes. Some of these mutations exert a dominant negative effect on wild-type channels.