Connexin 40 in atrial fibrillation: pathophysiological roles and regulatory mechanisms

TL;DR

This paper reviews how Connexin 40 affects atrial fibrillation by influencing heart cell communication and electrical signaling.

Contribution

The paper systematically examines how Cx40 genetic variations and protein degradation pathways contribute to atrial fibrillation.

Findings

Cx40 genetic polymorphisms influence cardiac electrophysiology and atrial structural remodelling.

Ubiquitination-mediated degradation regulates Cx40 stability in atrial fibrillation.

Cx40 dysregulation disrupts atrial electrical conduction and contributes to AF pathogenesis.

Abstract

Atrial fibrillation (AF), the most prevalent clinical atrial arrhythmia, arises from complex dysregulation of multicellular signalling pathways and molecular networks. Recent advances in cardiac electrophysiology have identified the atrial-specific gap junction protein Connexin 40 (Cx40) as a pivotal regulator of intercellular communication and cardiac electrical synchronization in AF pathogenesis. Aberrant Cx40 expression significantly disrupts atrial electrical conduction, yet its precise regulatory mechanisms remain incompletely understood. This review systematically examines the multifaceted roles of Cx40 in AF development, particularly focusing on how Cx40 genetic polymorphisms influence cardiac electrophysiology and promote atrial structural remodelling. Furthermore, we elucidate the ubiquitination-mediated protein degradation pathways governing Cx40 stability. These insights advance our understanding of AF pathophysiology and highlight potential therapeutic targets for precision arrhythmia management.

Figures