{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:30:33Z","timestamp":1789194633420,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,5,21]],"date-time":"2017-05-21T00:00:00Z","timestamp":1495324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000764","name":"Kings College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000764","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010872","name":"King's College Hospital NHS Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010872","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006133","name":"Anders Jahres Fond til Vitenskapens Fremme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006133","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005366","name":"Universitetet i Oslo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004941","name":"Guy's and St Thomas' NHS Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004941","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,6,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>At the cellular level cardiac hypertrophy causes remodelling, leading to changes in ionic channel, pump and exchanger densities and kinetics.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Previous studies have focused on quantifying changes in channels, pumps and exchangers without quantitatively linking these changes with emergent cellular scale functionality.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Two biophysical cardiac cell models were created, parameterized and validated and are able to simulate electrophysiology and calcium dynamics in myocytes from control sham operated rats and aortic\u2010banded rats exhibiting diastolic dysfunction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The contribution of each ionic pathway to the calcium kinetics was calculated, identifying the L\u2010type Ca<jats:sup>2+<\/jats:sup> channel and sarco\/endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>ATPase as the principal regulators of systolic and diastolic Ca<jats:sup>2+<\/jats:sup>, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Results show that the ability to dynamically change systolic Ca<jats:sup>2+<\/jats:sup>, through changes in expression of key Ca<jats:sup>2+<\/jats:sup> modelling protein densities, is drastically reduced following the aortic banding procedure; however the cells are able to compensate Ca<jats:sup>2+<\/jats:sup> homeostasis in an efficient way to minimize systolic dysfunction.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Elevated left ventricular afterload leads to myocardial hypertrophy, diastolic dysfunction, cellular remodelling and compromised calcium dynamics. At the cellular scale this remodelling of the ionic channels, pumps and exchangers gives rise to changes in the Ca<jats:sup>2+<\/jats:sup> transient. However, the relative roles of the underlying subcellular processes and the positive or negative impact of each remodelling mechanism are not fully understood. Biophysical cardiac cell models were created to simulate electrophysiology and calcium dynamics in myocytes from control rats (SHAM) and aortic\u2010banded rats exhibiting diastolic dysfunction. The model parameters and framework were validated and the fitted parameters demonstrated to be unique for explaining our experimental data. The contribution of each ionic pathway to the calcium kinetics was calculated, identifying the L\u2010type Ca<jats:sup>2+<\/jats:sup> channel (LCC) and the sarco\/endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>\u2010ATPase (SERCA) as the principal regulators of systolic and diastolic Ca<jats:sup>2+<\/jats:sup>, respectively. In the aortic banding model, the sensitivity of systolic Ca<jats:sup>2+<\/jats:sup> to LCC density and diastolic Ca<jats:sup>2+<\/jats:sup> to SERCA density decreased by 16\u2010fold and increased by 23%, respectively, relative to the SHAM model. The energy cost of ionic homeostasis is maintained across the two models. The models predict that changes in ionic pathway densities in compensated aortic banding rats maintain Ca<jats:sup>2+<\/jats:sup> function and efficiency. The ability to dynamically alter systolic function is significantly diminished, while the capacity to maintain diastolic Ca<jats:sup>2+<\/jats:sup> is moderately increased.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp273879","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T22:20:10Z","timestamp":1495578010000},"page":"3867-3889","source":"Crossref","is-referenced-by-count":13,"title":["Compensatory and decompensatory alterations in cardiomyocyte Ca<sup>2+<\/sup> dynamics in hearts with diastolic dysfunction following aortic banding"],"prefix":"10.1113","volume":"595","author":[{"given":"Sara","family":"Gattoni","sequence":"first","affiliation":[{"name":"King's College London, Department of Biomedical Engineering and Imaging Sciences, St Thomas\u2019 Hospital, 4th floor North Wing The Rayne Institute  London SE1 7EH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5smund Treu","family":"R\u00f8e","sequence":"additional","affiliation":[{"name":"Institute for Experimental Medical Research Oslo University Hospital and University of Oslo  Oslo Norway"},{"name":"K. 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