{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T02:18:17Z","timestamp":1784081897252,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,10,13]],"date-time":"2019-10-13T00:00:00Z","timestamp":1570924800000},"content-version":"am","delay-in-days":335,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T00:00:00Z","timestamp":1541980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CMMI\u20101562587"],"award-info":[{"award-number":["CMMI\u20101562587"]}],"id":[{"id":"10.13039\/100000001","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":[[2019,2]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Prior studies have shown variation in the functional properties of cardiomyocytes isolated from different regions of the left ventricular myocardium.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We found that these region\u2010dependent variations vanish below a tissue volume of \u223c7 mm<jats:sup>3<\/jats:sup> in the adult rat myocardium, revealing a fixed level of intrinsic relaxation rate heterogeneity that is independent of tissue volume.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Within these microscopically varying cell populations, fast\u2010relaxing cells were shown to have elevated phosphorylated troponin I compared to slow\u2010relaxing cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Relaxation rate was also correlated with cardiomyocyte length, in that slow\u2010relaxing cells were longer than fast\u2010relaxing cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results show a new relationship between cardiomyocyte morphology and myofilament relaxation, and suggest that functional diversity among individual myocytes at the microscale may contribute to bulk relaxation of the myocardium.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The mean contractility and calcium handling properties of cardiomyocytes isolated from different regions of the ventricular myocardium are known to vary significantly. We designed experiments to quantify the variance in contractile properties among cells within the same myocardial region. Longitudinal strips of myocardial tissue were excised from the epicardial left ventricular free walls of adult Sprague\u2013Dawley rats and then treated with collagenase to isolate individual myocytes. Cardiomyocytes were characterized by measuring sarcomere length changes and calcium transients during electrical pacing. Variance of the time from peak sarcomere shortening to 50% re\u2010lengthening (RT<jats:sub>50<\/jats:sub>) was assessed in each cell population. Isolating cells from progressively shorter strips allowed an estimate of the myocardial volume below which regional variation vanished and only microscale heterogeneity remained (\u223c7 mm<jats:sup>3<\/jats:sup>). The SD of RT<jats:sub>50<\/jats:sub> within this myocardial volume was 28% of the mean. In a series of follow\u2010up experiments, RT<jats:sub>50<\/jats:sub> was shown to correlate significantly with resting myocyte length, suggesting a connection between cell morphology and intrinsic relaxation behaviour. To explore the mechanistic basis of varying RT<jats:sub>50<\/jats:sub>, a novel single\u2010cell aspirator was employed to collect small batches of cardiomyocytes grouped according to their relaxation rates (fast or slow). Western blot analysis of the two groups revealed significantly elevated troponin I phosphorylation in fast\u2010relaxing cells. Our observations suggest that cell\u2010to\u2010cell heterogeneity of active contractile properties is substantial, with implications for how we understand myocardial relaxation and design drug therapies intended to alter relaxation rate.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp276718","type":"journal-article","created":{"date-parts":[[2018,10,13]],"date-time":"2018-10-13T12:34:11Z","timestamp":1539434051000},"page":"711-722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Diverse relaxation rates exist among rat cardiomyocytes isolated from a single myocardial region"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-7271","authenticated-orcid":false,"given":"J. Alexander","family":"Clark","sequence":"first","affiliation":[{"name":"Biomedical Engineering Yale University  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1527-0770","authenticated-orcid":false,"given":"Stuart G.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Yale University  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04844"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.2.H610"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2015.12.024"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00797.2012"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00748.2003"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2015.05.010"},{"key":"e_1_2_5_8_1","first-page":"jbc","article-title":"Long\u2010term ablation of PKA\u2010mediated cardiac troponin I phosphorylation leads to excitation\u2010contraction uncoupling and diastolic dysfunction in a knock\u2010in mouse model of hypertrophic cardiomyopathy","author":"Dweck D","year":"2014","journal-title":"J Biol Chem"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070919"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.190504"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071359"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2012.01611.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-08-1296"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2009.2017376"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-016-1593-7"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00252.2012"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw026"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.03.005"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1611184114"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1993.264.4.H1048"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11682"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2003.00187.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.76.6.1028"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP276718","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP276718","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP276718","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1113\/JP276718","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP276718","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T22:58:24Z","timestamp":1694386704000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP276718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,12]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1113\/JP276718"],"URL":"https:\/\/doi.org\/10.1113\/jp276718","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,12]]},"assertion":[{"value":"2018-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}