Combining experimental and computational approaches to investigate arrhythmogenic consequences of connexin hemichannel opening in the heart.

The project starts with the in depth characterization of Cx43 hemichannels as channels commanded by

voltage, intracellular Ca2+ and mechanical forces (WP1). These data will be incorporated into an existing and

well acknowledged multi-scale model of the heart aiming to predict the effects of hemichannel opening on three

well chosen arrhythmia conditions described in WP2, WP3 & WP4. In these WPs, we test the computational

predictions in experimental work.

WP2 focuses on the effect of hemichannels on arrhythmia initiation via the mechanisms of early

afterdepolarization (EAD), delayed afterdepolarization (DAD) and re-entry.

WP3 focuses on the effect of hemichannels on beat-to-beat variation of repolarization, which is one of the

most promising biomarkers allowing to predict the onset of an immenent arrhythmia.

WP4 focuses on the influence of hemichannels on the success of a defibrillation intervention.