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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Pharmacological or genetic ablation of the NAADP pathway inhibits the spontaneous beating rate response to \u03b2-adrenergic stimulation in intact SAN. We found intracellular signalling microdomains between lysosomes and neighbouring 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\u2032-5\u2032-cyclic adenosine monophosphate (cAMP) in response to lysosomal signalling, adding a novel trigger for cyclic nucleotide signalling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings support the hypothesis that lysosomal Ca2+ signalling contributes to regulation of cardiomyocyte cAMP levels and pacemaker activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag207","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:21:12Z","timestamp":1789791672000},"source":"Crossref","is-referenced-by-count":1,"title":["Lysosomal signalling pathways influence heart rhythm, and regulate atrial function"],"prefix":"10.1093","author":[{"given":"Emily","family":"Akerman","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Oxford , Oxford OX1 3QT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A","family":"Capel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford , Oxford OX1 3QT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva A","family":"Rog-Zielinska","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center and Faculty of Medicine, University of Freiburg , 79110 Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-3166","authenticated-orcid":false,"given":"Annika","family":"Winbo","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Auckland , Auckland 1142 ,","place":["New 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