{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:50:55Z","timestamp":1777877455417,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003513","name":"University of Surrey","doi-asserted-by":"crossref","award":["Kamalan Jeevaratnam"],"award-info":[{"award-number":["Kamalan Jeevaratnam"]}],"id":[{"id":"10.13039\/501100003513","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alpha-synuclein is associated with neurodegeneration in Parkinson's disease (PD). Recent studies have increasingly recognized incidences of cardiac complaints in PD patients. In particular, the occurrence of arrhythmias in PD patients may indicate potential electrophysiological alterations in the heart. Alpha-synuclein aggregates have been known to have disruptive effects on cell membranes. However, the effect of alpha-synuclein on the heart and sympathetic neuronal tissues remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigated the electrophysiological effects of alpha-synuclein aggregates in myocardium and cardiac sympathetic nervous system, potentially reflecting cardiac electrophysiological alteration in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We measured the\n                      <jats:italic toggle=\"yes\">in situ<\/jats:italic>\n                      sodium and potassium currents from murine ventricular myocardium and stellate ganglia using the loose patch clamp technique. The tissues were exposed to bioactive alpha-synuclein aggregates, and currents were measured under three different conditions: baseline, alpha-synuclein treatment, and wash out.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The experiments showed that alpha-synuclein aggregates altered the maximum cardiac sodium current (\n                      <jats:italic toggle=\"yes\">I<\/jats:italic>\n                      <jats:sub>Na(Max)<\/jats:sub>\n                      ) (ANOVA, p\u2009&lt;\u20090.008) and affected its gating properties for channel activation (ANOVA\n                      <jats:italic toggle=\"yes\">F<\/jats:italic>\n                      <jats:sub>2,54<\/jats:sub>\n                      \u2009=\u20096.408,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.003) and inactivation (\n                      <jats:italic toggle=\"yes\">F<\/jats:italic>\n                      <jats:sub>2, 67<\/jats:sub>\n                      \u2009=\u20096.32,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.003). The alpha-synuclein aggregates also reduced the maximum outward potassium current (\n                      <jats:italic toggle=\"yes\">I<\/jats:italic>\n                      <jats:sub>K(Max)<\/jats:sub>\n                      ) during channel activation (\n                      <jats:italic toggle=\"yes\">F<\/jats:italic>\n                      <jats:sub>2, 77<\/jats:sub>\n                      \u2009=\u20096.02,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.002). However, the alpha-synuclein aggregates did not affect the ionic currents in the stellate ganglia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results demonstrate that extracellular alpha-synuclein aggregates can inhibit ventricular but not stellate ganglion ionic currents, suggesting a differential sensitivity between the myocardium and the stellate ganglia, and indicating a cardiac-specific toxicity of alpha-synuclein on cardiac electrophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1877718x251365239","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:40:15Z","timestamp":1756384815000},"page":"1194-1207","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["In situ exogenous alpha-synuclein aggregates inhibit murine ventricular voltage-gated inward sodium and outward potassium currents"],"prefix":"10.1177","volume":"15","author":[{"given":"Bonn","family":"Lee","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine, Faculty of Health and Medical Science, University of Surrey, Surrey, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiraz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Faculty of Health and Medical Science, University of Surrey, Surrey, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0959-1455","authenticated-orcid":false,"given":"Charlotte E","family":"Edling","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Faculty of Health and Medical Science, University of Surrey, Surrey, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh R","family":"Matthews","sequence":"additional","affiliation":[{"name":"Physiological Laboratory, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9553-6112","authenticated-orcid":false,"given":"Christopher L-H","family":"Huang","sequence":"additional","affiliation":[{"name":"Physiological Laboratory, University of Cambridge, Cambridge, UK"},{"name":"Department of Biochemistry, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1453-4022","authenticated-orcid":false,"given":"Fiona EN","family":"LeBeau","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Faculty of Medical Sciences, University of Newcastle, Newcastle upon Tyne, UK"},{"name":"The Medical School, Framlington Place, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-388X","authenticated-orcid":false,"given":"Kamalan","family":"Jeevaratnam","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Faculty of Health and Medical Science, University of Surrey, Surrey, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00504-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6469"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar050073t"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100976108"},{"key":"e_1_3_3_9_2","first-page":"3269","article-title":"Nanomolar concentration of alpha-synuclein enhances dopaminergic neuronal survival via akt pathway","volume":"8","author":"Kim JY","year":"2013","unstructured":"Kim JY, Jeon BS, Kim HJ, et al. Nanomolar concentration of alpha-synuclein enhances dopaminergic neuronal survival via akt pathway. Neural Regen Res 2013; 8: 3269\u20133274.","journal-title":"Neural Regen Res"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8812"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600451"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80886-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.12.023"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181fd613b"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep02540"},{"key":"e_1_3_3_16_2","article-title":"Serological analysis of alpha-synuclein and NF-kappaB in Parkinson's disease patients","volume":"9","author":"Gupta V","year":"2015","unstructured":"Gupta V, Garg RK, Khattri S. Serological analysis of alpha-synuclein and NF-kappaB in Parkinson's disease patients. J Clin Diagn Res 2015; 9: BC01\u2013BC04.","journal-title":"J Clin Diagn Res"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-016-0072-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01866-2"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.042308.113313"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6160"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0537-x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4648"},{"key":"e_1_3_3_23_2","first-page":"4195","article-title":"Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson's disease","volume":"130","author":"Sarkar S","year":"2020","unstructured":"Sarkar S, Nguyen HM, Malovic E, et al. Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson's disease. J Clin Invest 2020; 130: 4195\u20134212.","journal-title":"J Clin Invest"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2012.08489.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042545"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi701275p"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612601"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2018.04.031"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.62"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlad001"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2012.07.005"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-223161"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.136399"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09770-1"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113311"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0236-9"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27183"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-492-6_11"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.15298"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2017.11.016"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.2c00251"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0234-12.2012"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201744617"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00262.2010"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00237"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004345200"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.01.029"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2775-9"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07576.x"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-025-00797-1"},{"key":"e_1_3_3_51_2","first-page":"718","article-title":"Adenosine A2A receptors modulate alpha-synuclein aggregation and toxicity","volume":"27","author":"Ferreira DG","year":"2017","unstructured":"Ferreira DG, Batalha VL, Vicente Miranda H, et al. Adenosine A2A receptors modulate alpha-synuclein aggregation and toxicity. Cereb Cortex 2017; 27: 718\u2013730.","journal-title":"Cereb Cortex"}],"container-title":["Journal of Parkinson\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1877718X251365239","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1877718X251365239","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1877718X251365239","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:51:55Z","timestamp":1777589515000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1877718X251365239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1177\/1877718X251365239"],"URL":"https:\/\/doi.org\/10.1177\/1877718x251365239","relation":{},"ISSN":["1877-7171","1877-718X"],"issn-type":[{"value":"1877-7171","type":"print"},{"value":"1877-718X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,28]]}}}