{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:09Z","timestamp":1792789089428,"version":"4.5.0"},"reference-count":203,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Heart Association","award":["26CDA1595551"],"award-info":[{"award-number":["26CDA1595551"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"award":["26CDA1595551"],"award-info":[{"award-number":["26CDA1595551"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cardiovascular disease is shaped not only by cardiomyocyte excitability but also by electrophysiological and membrane-signaling programs in cardiac fibroblasts, endothelial cells, mural cells, immune cells, and adipocytes. Recent single-cell RNA sequencing, spatial transcriptomic, and disease-atlas studies have revealed broad expression of ion-channel transcripts across these non-excitable cardiac cell populations. However, transcript detection alone does not establish functional channel activity, cell-state specificity, or therapeutic relevance. This narrative Review therefore focuses on mechanistically supported channel\u2013cell\u2013disease axes rather than providing an exhaustive catalogue of ion channels detected in cardiac non-myocytes. We synthesize evidence for mechanosensitive channels, transient receptor potential channels, calcium-entry pathways, acid-sensing channels, and potassium, sodium, and chloride channels, as well as connexin hemichannels and pannexin channels. We emphasize studies in which omics-based channel nomination is supported by functional validation through electrophysiology, Ca2+ imaging, mechanostimulation, pharmacological intervention, or cell-selective genetic perturbation. Particular attention is given to mechanisms linking mechanical stress, Ca2+ entry, membrane potential, cell-volume regulation, ATP release, immune activation, vascular tone, fibrosis, and metabolic dysfunction. We also identify key evidence gaps where expression-based observations require direct functional testing in human tissues and disease-relevant cardiac models. By distinguishing atlas-level association from causal channel function, this Review provides a framework for prioritizing non-myocyte ion-channel mechanisms as therapeutic targets in cardiovascular diseases.<\/jats:p>","DOI":"10.3390\/cells15191790","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:19:08Z","timestamp":1790842748000},"page":"1790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ion Channels in Cardiac Non-Excitable Cells: From Single-Cell Atlases to Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Weixuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"},{"name":"Bob and Corrine Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0579-5654","authenticated-orcid":false,"given":"Ashlyn A.","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"},{"name":"Bob and Corrine Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Bardallis","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"},{"name":"Bob and Corrine Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu Priya Bharathi","family":"Rajan","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"},{"name":"Bob and Corrine Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-1509","authenticated-orcid":false,"given":"Pengfei","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"},{"name":"Bob and Corrine Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1161\/CIRCEP.108.789081","article-title":"Cardiac ion channels","volume":"2","author":"Grant","year":"2009","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100951","DOI":"10.1016\/j.cossms.2021.100951","article-title":"Ion channel mediated mechanotransduction in immune cells","volume":"25","author":"Hamza","year":"2021","journal-title":"Curr. Opin. Solid State Mater. Sci."},{"key":"ref_3","first-page":"6550","article-title":"Mechanosensitive Ion Channels in Cardiovascular Physiology","volume":"20","author":"Teng","year":"2014","journal-title":"Exp. Clin. 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