Connexin 40 in atrial fibrillation: pathophysiological roles and regulatory mechanisms

Figures

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  Figure 1.. Schematic illustration of connexin hexameric assembly and gap junction ultrastructure. Gap Junction: Intercellular channels formed by docking of plasma membranes from adjacent cells, permitting exchange of small molecules and ions. Connexon: Hemichannel complex consisting of six connexin subunits. Channel patency is established when in the open conformation. Connexin:Tetratransmembrane protein regulating channel permeability through gating mechanisms. Created in BioRender. Yan [18]https://BioRender.com/hseenzr.

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  Figure 2.. The mechanism of atrial fibrillation pathogenesis associated with Cx40 dysfunction. Functional Cx40 deficiency → Disproportionate connexon clustering → Conduction delay/fragmentation → Focal APD dispersion & fibrotic remodeling → Re-entry via unidirectional block → Self-sustained AF circuitry. Created in BioRender. Yan (2025) https://BioRender.com/9m4t4py.

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  Figure 3.. Schematic diagram illustrating the proteasomal degradation of Cx40. UBQLN4 delivers ubiquitinated Cx40 to the proteasome for degradation, potentially impairing atrial gap junction coupling and contributing to AF pathogenesis. Created in BioRender. Yan (2025) https://BioRender.com/de7m2pi.