{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:47:18Z","timestamp":1761216438135},"reference-count":31,"publisher":"Proceedings of the National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,2,17]]},"abstract":"<jats:p>\n            Nonmuscle cells have almost ubiquitously evolved a mechanism to detect and prevent Ca\n            <jats:sup>2+<\/jats:sup>\n            store depletion\u2014store operated calcium entry. No such mechanism has, as yet, been reported in cardiac myocytes. However, it is conceivable that such a mechanism may play an important role in cardiac Ca\n            <jats:sup>2+<\/jats:sup>\n            homeostasis to ensure the availability of sufficient stored Ca\n            <jats:sup>2+<\/jats:sup>\n            to maintain normal excitation contraction coupling. We present data that confirms the presence of a mechanism that is able to monitor the Ca\n            <jats:sup>2+<\/jats:sup>\n            load of the SR and initiate a signaling process to accelerate Ca\n            <jats:sup>2+<\/jats:sup>\n            uptake by the SR when store depletion is detected. Depletion of SR Ca\n            <jats:sup>2+<\/jats:sup>\n            activates a protein kinase, the principal SR substrate of which is phospholamban. Phosphorylation of this SR protein promotes Ca\n            <jats:sup>2+<\/jats:sup>\n            pump activity and therefore store refilling. Furthermore, a protein kinase activity associated with the SR that is inhibited by Ca\n            <jats:sup>2+<\/jats:sup>\n            ions has been identified. We have measured lumenal [Ca\n            <jats:sup>2+<\/jats:sup>\n            ] by using a fluorescent Ca\n            <jats:sup>2+<\/jats:sup>\n            indicator and found that by initiating Ca\n            <jats:sup>2+<\/jats:sup>\n            uptake and increasing Ca\n            <jats:sup>2+<\/jats:sup>\n            load, we can inhibit the protein kinase activity associated with the SR. This confirms that a protein kinase, that is regulated by lumenal [Ca\n            <jats:sup>2+<\/jats:sup>\n            ], has been identified and represents part of a previously unidentified signalling cascade. This local feedback mechanism would allow the myocyte to detect and prevent SR Ca\n            <jats:sup>2+<\/jats:sup>\n            load depletion.\n          <\/jats:p>","DOI":"10.1073\/pnas.95.4.1484","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:35:50Z","timestamp":1027694150000},"page":"1484-1489","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Depletion of Ca\n            <sup>2+<\/sup>\n            from the sarcoplasmic reticulum of cardiac muscle prompts phosphorylation of phospholamban to  stimulate store refilling"],"prefix":"10.1073","volume":"95","author":[{"given":"Moninder Singh","family":"Bhogal","sequence":"first","affiliation":[{"name":"School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT United Kingdom"}]},{"given":"John","family":"Colyer","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Molecular 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