{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:20:59Z","timestamp":1790709659704,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["20\/305"],"award-info":[{"award-number":["20\/305"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/17\/14\/33085"],"award-info":[{"award-number":["RG\/17\/14\/33085"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Sympathetic hyperactivity associated with many primary cardiovascular diseases is pro\u2010arrhythmic and a key contributor to sudden cardiac death. Surgically removing the sympathetic stellate ganglion has demonstrated therapeutic potential in minimising cardiac arrhythmia, but there are off\u2010target risks prompting the need for more site\u2010specific non\u2010invasive approaches. Here we hypothesised that P2X3 purinergic receptors (P2X3R) may be a therapeutic target and play a role in the excessive sympathetic drive to the heart in cardiovascular disease. We investigated the role of P2X3R in the sympathetic stellate ganglion of Wistar and spontaneously hypertensive rats, and human\u2010induced pluripotent stem cell (hiPSC)\u2010derived sympathetic neurons, using a combination of immunohistochemistry, qRT\u2010PCR, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      calcium fluorescence imaging. Responses to ATP and P2X3R inhibition were investigated in intact stellate ganglion\u2013heart preparations\n                      <jats:italic>in situ<\/jats:italic>\n                      . We confirm expression of P2X3R in sympathetic neurons of rat stellate ganglia at mRNA and protein levels. P2X3R mRNA was upregulated in SHR stellate ganglia compared to Wistar. Activation of P2X3R increased [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:italic>\n                        <jats:sub>i<\/jats:sub>\n                      <\/jats:italic>\n                      in both isolated post\u2010ganglionic sympathetic stellate neurons and hiPSC\u2010derived sympathetic neurons, whereas microinjection of \u03b1\u03b2\u2010methylene ATP directly into right stellate ganglia induced tachycardia. Attenuation of these responses by a selective antagonist (AF353) indicated the tachycardia was P2X3R mediated. Inhibition of P2X3R rapidly restored the normal heart rhythm from sympathetic\u2010induced cardiac arrhythmia. We show that stellate ganglion P2X3R contribute to sympathetically mediated cardiac chronotropic regulation. Our findings highlight the potential for inhibition of P2X3R located in the sympathetic stellate ganglion as a promising novel therapeutic for sympathetic nervous system\u2010induced cardiac arrhythmias.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70303-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Sympathetic nerve overactivity is pro\u2010arrhythmic and a key contributor to left ventricular tachycardia and sudden cardiac death.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>P2X3 purinergic receptors are upregulated in stellate ganglia from prehypertensive rats.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Stellate ganglion P2X3 receptors mediate increases in neuronal intracellular calcium and heart rate.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Inhibiting P2X3 receptors rapidly and profoundly recovers normal heart rhythm from arrhythmia, highlighting the potential for inhibition of P2X3 receptors as a novel anti\u2010arrhythmic.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290004","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:00:41Z","timestamp":1767193241000},"page":"1067-1087","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti\u2010arrhythmic targeting of sympathetic stellate ganglion P2X3 receptors"],"prefix":"10.1113","volume":"604","author":[{"given":"Carol T.","family":"Bussey","sequence":"first","affiliation":[{"name":"Manaaki Manawa \u2013 The Centre for Heart Research, Department of Physiology, Faculty of Medical &amp; Health Sciences University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey","family":"Davis","sequence":"additional","affiliation":[{"name":"Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, Medical Sciences Division University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L.","family":"Bogert","sequence":"additional","affiliation":[{"name":"Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, Medical Sciences Division University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Dong","sequence":"additional","affiliation":[{"name":"Institute of Electrophysiology Henan Academy of Innovations in Medical Science  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, Medical Sciences Division University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichao","family":"Ma","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximillian C. 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