A study published in Cardiovascular Research titled 'Lysosomal signaling pathways influence heart rhythm, and regulate atrial function' reports that lysosomal signals play a role in controlling heart rhythm.

Funders include the Royal Society and Wellcome Trust, supporting this work.

In atrial fibrillation, the lysosomal pathway shows alterations such as larger lysosomes, disrupted spatial relationships with cellular structures, and changes in proteins related to lysosomal function and autophagy.

Compared with sinus rhythm, AF tissue exhibits larger lysosomes with altered interactions with other organelles and shifts in lysosome-associated proteins and autophagy pathways.

Researchers highlight the novelty of lysosomal involvement in cardiac rhythm control and the potential for new rhythm-disorder therapies.

The research blends animal models (mice, guinea pigs, rats, goats) with human lab-grown heart cells and human cardiac tissue to show lysosomal signaling influences heart function in health and disease.

Conducted by teams at the University of Liverpool and University of Oxford with collaborators, the study investigates lysosomal influence on heart rhythm across species and human models.

A new signaling pathway involves cAMP linking lysosomal calcium signals to heart rate regulation, with CaMKII and AC1 identified as likely near-lysosome participants in cardiomyocytes.

Lysosomes act as signaling centers in heart cells, contributing to the heart’s natural pacemaker by enabling faster beating when needed, beyond just recycling cellular components.

Lysosome-derived calcium signals raise cAMP levels to drive increased heart rate, illustrating a mechanism beyond traditional calcium signaling.

Findings point to targeting lysosomal signaling as a potential new approach for treating atrial fibrillation and related rhythm disorders, reflecting structural remodeling and altered intracellular signaling in AF.

Clinical implications suggest that modulating lysosomal signaling could offer novel therapies for atrial fibrillation.