{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:19:41Z","timestamp":1790320781626,"version":"4.1.0"},"reference-count":44,"publisher":"Portland Press Ltd.","issue":"20","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,30]]},"abstract":"<jats:p>Ryanodine receptors are responsible for the massive release of calcium from the sarcoplasmic reticulum that triggers heart muscle contraction. Maurocalcin (MCa) is a 33 amino acid peptide toxin known to target skeletal ryanodine receptor. We investigated the effect of MCa and its analog MCaE12A on isolated cardiac ryanodine receptor (RyR2), and showed that they increase RyR2 sensitivity to cytoplasmic calcium concentrations promoting channel opening and decreases its sensitivity to inhibiting calcium concentrations. By measuring intracellular Ca2+ transients, calcium sparks and contraction on cardiomyocytes isolated from adult rats or differentiated from human-induced pluripotent stem cells, we demonstrated that MCaE12A passively penetrates cardiomyocytes and promotes the abnormal opening of RyR2. We also investigated the effect of MCaE12A on the pacemaker activity of sinus node cells from different mice lines and showed that, MCaE12A improves pacemaker activity of sinus node cells obtained from mice lacking L-type Cav1.3 channel, or following selective pharmacologic inhibition of calcium influx via Cav1.3. Our results identify MCaE12A as a high-affinity modulator of RyR2 and make it an important tool for RyR2 structure-to-function studies as well as for manipulating Ca2+ homeostasis and dynamic of cardiac cells.<\/jats:p>","DOI":"10.1042\/bcj20200206","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T11:46:49Z","timestamp":1602244009000},"page":"3985-3999","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Maurocalcin and its analog MCaE12A facilitate Ca2+ mobilization in cardiomyocytes"],"prefix":"10.1042","volume":"477","author":[{"given":"Stephan","family":"De Waard","sequence":"first","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"},{"name":"LabEx Ion Channels Science and Therapeutics, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9rome","family":"Montnach","sequence":"additional","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charly","family":"Cortinovis","sequence":"additional","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olfa","family":"Chkir","sequence":"additional","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morteza","family":"Erfanian","sequence":"additional","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Hulin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Nantes, CHU Nantes, CNRS, INSERM, SFR Sant\u00e9, Inserm UMS 016, CNRS UMS 3556, F-44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gaborit","sequence":"additional","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Lemarchand","sequence":"additional","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Mesirca","sequence":"additional","affiliation":[{"name":"LabEx Ion Channels Science and Therapeutics, France"},{"name":"Institut de G\u00e9nomique Fonctionnelle, UNIV Montpellier, CNRS, Inserm, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Bidaud","sequence":"additional","affiliation":[{"name":"LabEx Ion Channels Science and Therapeutics, France"},{"name":"Institut de G\u00e9nomique Fonctionnelle, UNIV Montpellier, CNRS, Inserm, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo E.","family":"Mangoni","sequence":"additional","affiliation":[{"name":"LabEx Ion Channels Science and Therapeutics, France"},{"name":"Institut de G\u00e9nomique Fonctionnelle, UNIV Montpellier, CNRS, Inserm, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"De Waard","sequence":"additional","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"},{"name":"LabEx Ion Channels Science and Therapeutics, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-6425","authenticated-orcid":false,"given":"Michel","family":"Ronjat","sequence":"additional","affiliation":[{"name":"l'institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"},{"name":"LabEx Ion Channels Science and Therapeutics, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"2021112218143683200_BCJ-2020-0206C1","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1113\/jphysiol.1975.sp011026","article-title":"Contractions induced by a calcium-triggered release of calcium from the sarcoplasmic reticulum of single skinned cardiac cells","volume":"249","year":"1975","journal-title":"J. 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