Related Experiment Video
Updated: Sep 20, 2026

Isolation of Atrial Myocytes from Adult Mice
Published on: July 25, 2019
Lysosomal signaling pathways influence heart rhythm, and regulate atrial function
Emily Akerman1, Rebecca A Capel1, Eva A Rog-Zielinska2
1Department of Pharmacology, University of Oxford, Oxford, UK.
Aims:
In the heart, endogenous nicotinic acid adenine dinucleotide phosphate (NAADP) triggers lysosomal calcium (Ca2+) release to augment sarcoplasmic reticulum (SR) Ca2+ sequestration, producing larger Ca2+ transients. However, the role of lysosomal Ca2+ signals in pacemaker activity, a distinct Ca2+-operated function of the sinoatrial node (SAN), or in the atrial myocardium has not been investigated.
Methods And Results:
Pharmacological or genetic ablation of the NAADP pathway inhibits the spontaneous beating rate response to β-adrenergic stimulation in intact SAN. We found intracellular signaling microdomains between lysosomes and neighboring SR or mitochondria in mouse, and goat tissue. The spatial relationship between lysosomes and other Ca2+-handling organelles are altered in goat atrial fibrillation. Furthermore, we demonstrate atrial myocytes produce 3'-5'-cyclic adenosine monophosphate (cAMP) in response to lysosomal signaling, adding a novel trigger for cyclic nucleotide signaling.
Conclusions:
Our findings support the hypothesis that lysosomal Ca2+ signaling contributes to regulation of cardiomyocyte cAMP levels and pacemaker activity.
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