{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:48:26Z","timestamp":1788241706634,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a King\u2019s College London Graduate Training Award","award":["PG\/12\/34\/29557"],"award-info":[{"award-number":["PG\/12\/34\/29557"]}]},{"name":"a King\u2019s College London Graduate Training Award","award":["BB\/P005616\/1"],"award-info":[{"award-number":["BB\/P005616\/1"]}]},{"name":"a King\u2019s College London Graduate Training Award","award":["309046\/2016-5"],"award-info":[{"award-number":["309046\/2016-5"]}]},{"name":"a King\u2019s College London Graduate Training Award","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]},{"name":"British Heart Foundation","award":["PG\/12\/34\/29557"],"award-info":[{"award-number":["PG\/12\/34\/29557"]}]},{"name":"British Heart Foundation","award":["BB\/P005616\/1"],"award-info":[{"award-number":["BB\/P005616\/1"]}]},{"name":"British Heart Foundation","award":["309046\/2016-5"],"award-info":[{"award-number":["309046\/2016-5"]}]},{"name":"British Heart Foundation","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]},{"name":"Biotechnology and Biological Sciences Research Council","award":["PG\/12\/34\/29557"],"award-info":[{"award-number":["PG\/12\/34\/29557"]}]},{"name":"Biotechnology and Biological Sciences Research Council","award":["BB\/P005616\/1"],"award-info":[{"award-number":["BB\/P005616\/1"]}]},{"name":"Biotechnology and Biological Sciences Research Council","award":["309046\/2016-5"],"award-info":[{"award-number":["309046\/2016-5"]}]},{"name":"Biotechnology and Biological Sciences Research Council","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["PG\/12\/34\/29557"],"award-info":[{"award-number":["PG\/12\/34\/29557"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["BB\/P005616\/1"],"award-info":[{"award-number":["BB\/P005616\/1"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["309046\/2016-5"],"award-info":[{"award-number":["309046\/2016-5"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine the role of TRPC5 on cardiac function under basal conditions and during cardiac hypertrophy. Cardiovascular parameters were assessed in wild-type (WT) and global TRPC5 knockout (KO) mice. Despite no difference in blood pressure or activity, heart rate was significantly reduced in TRPC5 KO mice. Echocardiography imaging revealed an increase in stroke volume, but cardiac contractility was unaffected. The reduced heart rate persisted in isolated TRPC5 KO hearts, suggesting changes in basal cardiac pacing. Heart rate was further investigated by evaluating the reflex change following drug-induced pressure changes. The reflex bradycardic response following phenylephrine was greater in TRPC5 KO mice but the tachycardic response to SNP was unchanged, indicating an enhancement in the parasympathetic control of the heart rate. Moreover, the reduction in heart rate to carbachol was greater in isolated TRPC5 KO hearts. To evaluate the role of TRPC5 in cardiac pathology, mice were subjected to abdominal aortic banding (AAB). An exaggerated cardiac hypertrophy response to AAB was observed in TRPC5 KO mice, with an increased expression of hypertrophy markers, fibrosis, reactive oxygen species, and angiogenesis. This study provides novel evidence for a direct effect of TRPC5 on cardiac function. We propose that (1) TRPC5 is required for maintaining heart rate by regulating basal cardiac pacing and in response to pressure lowering, and (2) TRPC5 protects against pathological cardiac hypertrophy.<\/jats:p>","DOI":"10.3390\/biom14040442","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T06:57:34Z","timestamp":1712213854000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transient Receptor Potential Canonical 5 (TRPC5): Regulation of Heart Rate and Protection against Pathological Cardiac Hypertrophy"],"prefix":"10.3390","volume":"14","author":[{"given":"Pratish","family":"Thakore","sequence":"first","affiliation":[{"name":"BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 9NH, UK"},{"name":"School of Cancer and Pharmaceutical Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7574-2162","authenticated-orcid":false,"given":"James E.","family":"Clark","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisah A.","family":"Aubdool","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-5483","authenticated-orcid":false,"given":"Dibesh","family":"Thapa","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Starr","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Fraser","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Farrell-Dillon","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0567-2514","authenticated-orcid":false,"given":"Elizabeth S.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o, em Biotecnologia Aplicada \u00e0 Sa\u00fade da Crian\u00e7a e do Adolescente, Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Curitiba 80230-020, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"McFadzean","sequence":"additional","affiliation":[{"name":"School of Cancer and Pharmaceutical Sciences, King\u2019s College London, London SE1 9NH, UK"},{"name":"School of Bioscience Education, Faculty of Life Sciences & Medicine, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-8342","authenticated-orcid":false,"given":"Susan D.","family":"Brain","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"re3","DOI":"10.1126\/stke.2722005re3","article-title":"The TRP superfamily of cation channels","volume":"2005","author":"Montell","year":"2005","journal-title":"Sci. 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