{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:12:09Z","timestamp":1790172729794,"version":"4.1.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"49","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL085372"],"award-info":[{"award-number":["HL085372"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,12,6]]},"abstract":"Significance<\/jats:title>\n \n Calcium entry initiates contraction in cardiac myocytes, and altered expression of voltage-gated calcium channel 1.2 (Ca\n V<\/jats:sub>\n 1.2) causes heart failure in mice. Here we show that reducing \u03b2-adrenergic regulation of Ca\n V<\/jats:sub>\n 1.2 by mutation of a PKA site in the C-terminal domain causes age-related heart failure. Dual mutation of a nearby casein-kinase II phosphorylation site accelerated heart failure. The PKA level was increased; PKA-mediated phosphorylation of ryanodine receptor type-2, phospholamban, and troponin-I was increased; the calcium pool in the sarcoplasmic reticulum was increased; and the activity of the calcium-dependent phosphoprotein phosphatase calcineurin was persistently elevated. These changes in mice with a mutation at the PKA site Ser1700 (SA mice) suggest that compensatory mechanisms may initially enhance contractility but eventually cause increased sensitivity to cardiovascular stress and heart failure.\n <\/jats:p>","DOI":"10.1073\/pnas.1617116113","type":"journal-article","created":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T22:45:28Z","timestamp":1479509128000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["Loss of \u03b2-adrenergic\u2013stimulated phosphorylation of Ca\n V<\/sub>\n 1.2 channels on Ser1700 leads to heart failure"],"prefix":"10.1073","volume":"113","author":[{"given":"Linghai","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Washington, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao-Fu","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of 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