{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:11:40Z","timestamp":1774332700730,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T00:00:00Z","timestamp":1523664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/10\/91\/28644"],"award-info":[{"award-number":["PG\/10\/91\/28644"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/14\/65\/31055"],"award-info":[{"award-number":["PG\/14\/65\/31055"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/12\/10\/29802"],"award-info":[{"award-number":["RG\/12\/10\/29802"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Heart failure is associated with redistribution of L\u2010type Ca<jats:sup>2+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>) away from the t\u2010tubule membrane to the surface membrane of cardiac ventricular myocytes. However, the underlying mechanism and its dependence on severity of pathology (hypertrophy <jats:italic>versus<\/jats:italic> failure) are unclear.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Increasing severity of response to transverse aortic constriction, from hypertrophy to failure, was accompanied by graded loss of t\u2010tubular <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> and loss of regulation of <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> by caveolin\u00a03. Thus, the pathological loss of t\u2010tubular <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>, which contributes to impaired excitation\u2013contraction coupling and thereby cardiac function <jats:italic>in vivo<\/jats:italic>, appears to be attributable to loss of caveolin\u00a03\u2010dependent stimulation of t\u2010tubular <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Previous work has shown redistribution of L\u2010type Ca<jats:sup>2+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>) from the t\u2010tubules to the surface membrane of rat ventricular myocytes after myocardial infarction. However, whether this occurs in all species and in response to other insults, the relationship of this redistribution to the severity of the pathology, and the underlying mechanism, are unknown. We have therefore investigated the response of mouse hearts and myocytes to pressure overload induced by transverse aortic constriction (TAC). Male C57BL\/6 mice underwent TAC or equivalent sham operation 8\u00a0weeks before use. <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> and Ca<jats:sup>2+<\/jats:sup> transients were measured in isolated myocytes, and expression of caveolin\u00a03 (Cav3), junctophilin\u00a02 (Jph2) and bridging integrator\u00a01 (Bin1) was determined. C3SD peptide was used to disrupt Cav3 binding to its protein partners. Some animals showed cardiac hypertrophy in response to TAC with little evidence of heart failure, whereas others showed greater hypertrophy and pulmonary congestion. These graded changes were accompanied by graded cellular hypertrophy, t\u2010tubule disruption, decreased expression of Jph2 and Cav3, and decreased t\u2010tubular <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> density, with no change at the cell surface, and graded impairment of Ca<jats:sup>2+<\/jats:sup> release at t\u2010tubules. C3SD decreased <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> density in control but not in TAC myocytes. These data suggest that the graded changes in cardiac function and size that occur in response to TAC are paralleled by graded changes in cell structure and function, which will contribute to the impaired function observed <jats:italic>in vivo<\/jats:italic>. They also suggest that loss of t\u2010tubular <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> is attributable to loss of Cav3\u2010dependent stimulation of <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep086731","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T09:22:46Z","timestamp":1519377766000},"page":"652-665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Caveolin 3\u2010dependent loss of t\u2010tubular <i>I<\/i><sub>Ca<\/sub> during hypertrophy and heart failure in mice"],"prefix":"10.1113","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-6203","authenticated-orcid":false,"given":"Simon M.","family":"Bryant","sequence":"first","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cherrie H. T.","family":"Kong","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy J.","family":"Watson","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanne C.","family":"Gadeberg","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew F.","family":"James","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark B.","family":"Cannell","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7714-5900","authenticated-orcid":false,"given":"Clive H.","family":"Orchard","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503465103"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(03)00325-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00816.2006"},{"issue":"1","key":"e_1_2_7_5_1","first-page":"I11","article-title":"Voltage\u2010gated Ca2+ currents in the human pathophysiologic heart: A review","volume":"97","author":"Benitah J. 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