Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis.

ABSTRACT:

Aims

Atrial fibrillation (AF), the most prevalent clinical arrhythmia, is associated with atrial remodelling manifesting as acute and chronic alterations in expression, function, and regulation of atrial electrophysiological and Ca2+-handling processes. These AF-induced modifications crosstalk and propagate across spatial scales creating a complex pathophysiological network, which renders AF resistant to existing pharmacotherapies that predominantly target transmembrane ion channels. Developing innovative therapeutic strategies requires a systems approach to disentangle quantitatively the pro-arrhythmic contributions of individual AF-induced alterations.

Methods and results

Here, we built a novel computational framework for simulating electrophysiology and Ca2+-handling in h

SUBMITTER: Ni H 

PROVIDER: S-EPMC11318383 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature