{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:18:21Z","timestamp":1791980301887,"version":"4.4.0"},"reference-count":77,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR 152, Project-ID 239283807"],"award-info":[{"award-number":["TRR 152, Project-ID 239283807"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR 2289"],"award-info":[{"award-number":["FOR 2289"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1118"],"award-info":[{"award-number":["SFB 1118"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1326"],"award-info":[{"award-number":["GRK1326"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DIAMICOM, GRK 1874"],"award-info":[{"award-number":["DIAMICOM, GRK 1874"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FL 153\/10-2"],"award-info":[{"award-number":["FL 153\/10-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pathological cardiac remodeling correlates with chronic neurohumoral stimulation and abnormal Ca2+ signaling in cardiomyocytes. Store-operated calcium entry (SOCE) has been described in adult and neonatal murine cardiomyocytes, and Orai1 proteins act as crucial ion-conducting constituents of this calcium entry pathway that can be engaged not only by passive Ca2+ store depletion but also by neurohumoral stimuli such as angiotensin-II. In this study, we, therefore, analyzed the consequences of Orai1 deletion for cardiomyocyte hypertrophy in neonatal and adult cardiomyocytes as well as for other features of pathological cardiac remodeling including cardiac contractile function in vivo. Cellular hypertrophy induced by angiotensin-II in embryonic cardiomyocytes from Orai1-deficient mice was blunted in comparison to cells from litter-matched control mice. Due to lethality of mice with ubiquitous Orai1 deficiency and to selectively analyze the role of Orai1 in adult cardiomyocytes, we generated a cardiomyocyte-specific and temporally inducible Orai1 knockout mouse line (Orai1CM\u2013KO). Analysis of cardiac contractility by pressure-volume loops under basal conditions and of cardiac histology did not reveal differences between Orai1CM\u2013KO mice and controls. Moreover, deletion of Orai1 in cardiomyocytes in adult mice did not protect them from angiotensin-II-induced cardiac remodeling, but cardiomyocyte cross-sectional area and cardiac fibrosis were enhanced. These alterations in the absence of Orai1 go along with blunted angiotensin-II-induced upregulation of the expression of Myoz2 and a lack of rise in angiotensin-II-induced STIM1 and Orai3 expression. In contrast to embryonic cardiomyocytes, where Orai1 contributes to the development of cellular hypertrophy, the results obtained from deletion of Orai1 in the adult myocardium reveal a protective function of Orai1 against the development of angiotensin-II-induced cardiac remodeling, possibly involving signaling via Orai3\/STIM1-calcineurin-NFAT related pathways.<\/jats:p>","DOI":"10.3390\/cells9051092","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T01:29:15Z","timestamp":1588123755000},"page":"1092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cardiomyocyte-Specific Deletion of Orai1 Reveals Its Protective Role in Angiotensin-II-Induced Pathological Cardiac Remodeling"],"prefix":"10.3390","volume":"9","author":[{"given":"Sebastian","family":"Segin","sequence":"first","affiliation":[{"name":"Pharmakologisches Institut, Ruprecht-Karls-Universit\u00e4t Heidelberg, INF 366, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Berlin","sequence":"additional","affiliation":[{"name":"Pharmakologisches Institut, Ruprecht-Karls-Universit\u00e4t Heidelberg, INF 366, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin","family":"Richter","sequence":"additional","affiliation":[{"name":"Pharmakologisches Institut, Ruprecht-Karls-Universit\u00e4t Heidelberg, INF 366, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7571-3732","authenticated-orcid":false,"given":"Rebekka","family":"Medert","sequence":"additional","affiliation":[{"name":"Pharmakologisches Institut, Ruprecht-Karls-Universit\u00e4t Heidelberg, INF 366, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit","family":"Flockerzi","sequence":"additional","affiliation":[{"name":"Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Worley","sequence":"additional","affiliation":[{"name":"The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1387-2636","authenticated-orcid":false,"given":"Marc","family":"Freichel","sequence":"additional","affiliation":[{"name":"Pharmakologisches Institut, Ruprecht-Karls-Universit\u00e4t Heidelberg, INF 366, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0673-7583","authenticated-orcid":false,"given":"Juan E.","family":"Camacho Londo\u00f1o","sequence":"additional","affiliation":[{"name":"Pharmakologisches Institut, Ruprecht-Karls-Universit\u00e4t Heidelberg, INF 366, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrcardio.2016.163","article-title":"Neurohormonal activation in heart failure with reduced ejection fraction","volume":"14","author":"Hartupee","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1152\/physrev.00003.2005","article-title":"Mammalian G Proteins and Their Cell Type Specific Functions","volume":"85","author":"Wettschureck","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.yjmcc.2011.05.001","article-title":"Unraveling the secrets of a double life: Contractile versus signaling Ca2+ in a cardiac myocyte","volume":"52","author":"Goonasekera","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1161\/CIRCRESAHA.113.301651","article-title":"Mechanisms of altered Ca2+ handling in heart failure","volume":"113","author":"Luo","year":"2013","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/978-3-319-57732-6_25","article-title":"Cardiac Remodeling and Disease: SOCE and TRPC Signaling in Cardiac Pathology","volume":"993","author":"Eder","year":"2017","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Freichel, M., Berlin, M., Sch\u00fcrger, A., Mathar, I., Bacmeister, L., Medert, R., Frede, W., Marx, A., Segin, S., and Londo\u00f1o, J.E.C. (2017). TRP Channels in the Heart. Methods for Neural Ensemble Recordings, Informa UK Limited.","DOI":"10.4324\/9781315152837-9"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3389\/fcvm.2017.00056","article-title":"TRPC3 Channels in Cardiac Fibrosis","volume":"4","author":"Oda","year":"2017","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.pbiomolbio.2017.06.010","article-title":"Role of TRPC3 and TRPC6 channels in the myocardial response to stretch: Linking physiology and pathophysiology","volume":"130","author":"Yamaguchi","year":"2017","journal-title":"Prog. Biophys. Mol. Boil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1093\/eurheartj\/ehv250","article-title":"A background Ca2+ entry pathway mediated by TRPC1\/TRPC4 is critical for development of pathological cardiac remodelling","volume":"36","author":"Tian","year":"2015","journal-title":"Eur. Hear. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1152\/physrev.1997.77.4.901","article-title":"Store depletion and calcium influx","volume":"77","author":"Parekh","year":"1997","journal-title":"Physiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1152\/physrev.00057.2003","article-title":"Store-Operated Calcium Channels","volume":"85","author":"Parekh","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature04702","article-title":"A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function","volume":"441","author":"Feske","year":"2006","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nature05122","article-title":"Orai1 is an essential pore subunit of the CRAC channel","volume":"443","author":"Prakriya","year":"2006","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1126\/science.1127883","article-title":"CRACM1 Is a Plasma Membrane Protein Essential for Store-Operated Ca2+ Entry","volume":"312","author":"Vig","year":"2006","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9357","DOI":"10.1073\/pnas.0603161103","article-title":"Genome-wide RNAi screen of Ca2+ influx identifies genes that regulate Ca2+ release-activated Ca2+ channel activity","volume":"103","author":"Zhang","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1126\/science.1228757","article-title":"Crystal structure of the calcium release\u2013activated calcium channel Orai","volume":"338","author":"Hou","year":"2012","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19375","DOI":"10.1074\/jbc.M701962200","article-title":"Murine ORAI2 Splice Variants Form Functional Ca2+Release-activated Ca2+(CRAC) Channels","volume":"282","author":"Gross","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ceca.2019.03.004","article-title":"CRAC channels and disease \u2013 From human CRAC channelopathies and animal models to novel drugs","volume":"80","author":"Feske","year":"2019","journal-title":"Cell Calcium"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/nature04147","article-title":"STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane","volume":"437","author":"Zhang","year":"2005","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35855","DOI":"10.1074\/jbc.M608247200","article-title":"Stored Ca2+ Depletion-induced Oligomerization of Stromal Interaction Molecule 1 (STIM1) via the EF-SAM Region: An Initiation Mechanism for Capacitive Ca2+ Entry","volume":"281","author":"Stathopulos","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.cub.2005.05.055","article-title":"STIM Is a Ca2+ Sensor Essential for Ca2+-Store-Depletion-Triggered Ca2+ Influx","volume":"15","author":"Liou","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1083\/jcb.200502019","article-title":"STIM1, an essential and conserved component of store-operated Ca2+ channel function","volume":"169","author":"Roos","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.yjmcc.2011.11.003","article-title":"STIM1-dependent store-operated Ca2+ entry is required for pathological cardiac hypertrophy","volume":"52","author":"Luo","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1161\/CIRCULATIONAHA.111.031229","article-title":"Critical role for stromal interaction molecule 1 in cardiac hypertrophy","volume":"124","author":"Hulot","year":"2011","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.yjmcc.2010.01.020","article-title":"Orai1 and Stim1 regulate normal and hypertrophic growth in cardiomyocytes","volume":"48","author":"Salz","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"H1124","DOI":"10.1152\/ajpheart.00162.2003","article-title":"Adult rat cardiomyocytes exhibit capacitative calcium entry","volume":"286","author":"Hunton","year":"2004","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbrc.2011.10.133","article-title":"Store-operated calcium entry is present in HL-1 cardiomyocytes and contributes to resting calcium","volume":"416","author":"Touchberry","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14266","DOI":"10.1074\/jbc.M107167200","article-title":"Capacitative Calcium Entry Contributes to Nuclear Factor of Activated T-cells Nuclear Translocation and Hypertrophy in Cardiomyocytes","volume":"277","author":"Hunton","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1096\/fj.05-5560com","article-title":"Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart","volume":"20","author":"Nakayama","year":"2006","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1161\/CIRCRESAHA.107.152181","article-title":"Store-Operated Ca2+Influx and Expression of TRPC Genes in Mouse Sinoatrial Node","volume":"100","author":"Ju","year":"2007","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1242\/jcs.090464","article-title":"Orai1 deficiency leads to heart failure and skeletal myopathy in zebrafish","volume":"125","author":"Dolatabadi","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1159\/000490036","article-title":"Overexpression of SARAF Ameliorates Pressure Overload\u2013Induced Cardiac Hypertrophy Through Suppressing STIM1-Orai1 in Mice","volume":"47","author":"Dai","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2741\/S406","article-title":"STIM1 and Orai in cardiac hypertrophy and vascular proliferative diseases","volume":"5","author":"Benard","year":"2013","journal-title":"Front. Biosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"H446","DOI":"10.1152\/ajpheart.00104.2013","article-title":"STIM1\/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology","volume":"305","author":"Collins","year":"2013","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_35","first-page":"9","article-title":"The Complex Role of Store Operated Calcium Entry Pathways and Related Proteins in the Function of Cardiac, Skeletal and Vascular Smooth Muscle Cells","volume":"9","author":"Ribas","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ceca.2018.11.008","article-title":"SOCE and STIM1 signaling in the heart: Timing and location matter","volume":"77","author":"Rosenberg","year":"2019","journal-title":"Cell Calcium"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5209","DOI":"10.1128\/MCB.00360-08","article-title":"Hair Loss and Defective T- and B-Cell Function in Mice Lacking ORAI1","volume":"28","author":"Gwack","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"bio049999","DOI":"10.1242\/bio.049999","article-title":"Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart","volume":"9","author":"Petersen","year":"2020","journal-title":"Biol. Open"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35","DOI":"10.4161\/chan.26581","article-title":"The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy","volume":"8","author":"Horton","year":"2013","journal-title":"Channels"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"13394","DOI":"10.1074\/jbc.M115.693911","article-title":"Transient Receptor Potential Canonical (TRPC)\/Orai1-dependent Store-operated Ca2+Channels","volume":"291","author":"Sabourin","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1002\/stem.2118","article-title":"Nitric Oxide-cGMP-PKG Pathway Acts on Orai1 to Inhibit the Hypertrophy of Human Embryonic Stem Cell-Derived Cardiomyocytes","volume":"33","author":"Wang","year":"2015","journal-title":"Stem Cells"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3389\/fphar.2017.00222","article-title":"Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy","volume":"8","author":"Zheng","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.jaci.2009.10.007","article-title":"ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasia","volume":"124","author":"McCarl","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cmet.2017.02.007","article-title":"Orai1-Mediated Antimicrobial Secretion from Pancreatic Acini Shapes the Gut Microbiome and Regulates Gut Innate Immunity","volume":"25","author":"Ahuja","year":"2017","journal-title":"Cell Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1093\/nar\/23.24.5080","article-title":"A cre -transgenic mouse strain for the ubiquitous deletion of loxP -flanked gene segments including deletion in germ cells","volume":"23","author":"Schwenk","year":"1995","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1161\/CIRCULATIONAHA.112.109256","article-title":"G13-Mediated Signaling Pathway Is Required for Pressure Overload-Induced Cardiac Remodeling and Heart Failure","volume":"126","author":"Takefuji","year":"2012","journal-title":"Circulation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/dvg.20335","article-title":"A global double-fluorescent Cre reporter mouse","volume":"45","author":"Muzumdar","year":"2007","journal-title":"Genes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1038\/nprot.2008.138","article-title":"Measurement of cardiac function using pressure\u2013volume conductance catheter technique in mice and rats","volume":"3","author":"Pacher","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fcvm.2019.00036","article-title":"Assessment of PEEP-Ventilation and the Time Point of Parallel-Conductance Determination for Pressure-Volume Analysis Under \u03b2-Adrenergic Stimulation in Mice","volume":"6","author":"Bacmeister","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.ceca.2007.05.014","article-title":"Primary structure, chromosomal localization and expression in immune cells of the murine ORAI and STIM genes","volume":"42","author":"Wissenbach","year":"2007","journal-title":"Cell Calcium"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ceca.2019.01.002","article-title":"Methylglyoxal evokes acute Ca2+ transients in distinct cell types and increases agonist-evoked Ca2+ entry in endothelial cells via CRAC channels","volume":"78","author":"Sachdeva","year":"2019","journal-title":"Cell Calcium"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ceca.2011.04.002","article-title":"STIM and Orai in platelet function","volume":"50","author":"Braun","year":"2011","journal-title":"Cell Calcium"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cheng, K.T., Liu, X., Ong, H.L., Swaim, W., and Ambudkar, I.S. (2011). Local Ca\u00b2+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca\u00b2+ signals required for specific cell functions. PLoS Biol., 9.","DOI":"10.1371\/journal.pbio.1001025"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1074\/jbc.M110.179010","article-title":"Cellular and Molecular Mechanisms of Autosomal Dominant Form of Progressive Hearing Loss, DFNA2*","volume":"286","author":"Kim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1161\/CIRCRESAHA.109.198416","article-title":"Avoidance of transient cardiomyopathy in cardiomyocyte-targeted tamoxifen-induced MerCreMer gene deletion models","volume":"105","author":"Koitabashi","year":"2009","journal-title":"Circ. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"25372","DOI":"10.1038\/srep25372","article-title":"STIM1-dependent Ca2+ microdomains are required for myofilament remodeling and signaling in the heart","volume":"6","author":"Parks","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1126\/science.1191027","article-title":"The CRAC Channel Activator STIM1 Binds and Inhibits L-Type Voltage-Gated Calcium Channels","volume":"330","author":"Park","year":"2010","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1126\/science.1191086","article-title":"The Calcium Store Sensor, STIM1, Reciprocally Controls Orai and CaV1.2 Channels","volume":"330","author":"Wang","year":"2010","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"H1231","DOI":"10.1152\/ajpheart.00075.2014","article-title":"Stromal interaction molecule 1 is essential for normal cardiac homeostasis through modulation of ER and mitochondrial function","volume":"306","author":"Collins","year":"2014","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"H1014","DOI":"10.1152\/ajpheart.00544.2018","article-title":"Novel role of the ER\/SR Ca2+ sensor STIM1 in the regulation of cardiac metabolism","volume":"316","author":"Collins","year":"2019","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/cvr\/cvu207","article-title":"Emergence of Orai3 activity during cardiac hypertrophy","volume":"105","author":"Saliba","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1161\/res.125.suppl_1.922","article-title":"Abstract 922: Cardiac-specific Deletion of Orai3 Channel Causes Dilated Cardiomyopathy","volume":"125","author":"Mancarella","year":"2019","journal-title":"Circ. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ceca.2017.11.004","article-title":"Deletion of Orai2 augments endogenous CRAC currents and degranulation in mast cells leading to enhanced anaphylaxis","volume":"71","author":"Tsvilovskyy","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14714","DOI":"10.1038\/ncomms14714","article-title":"ORAI2 modulates store-operated calcium entry and T cell-mediated immunity","volume":"8","author":"Vaeth","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/ni1550","article-title":"Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels","volume":"9","author":"Vig","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1161\/CIRCULATIONAHA.118.038891","article-title":"Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca 2+ Handling After Pressure Overload","volume":"141","author":"Bartoli","year":"2020","journal-title":"Circ."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1161\/01.CIR.97.19.1952","article-title":"Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor knockout mice","volume":"97","author":"Harada","year":"1998","journal-title":"Circulation"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1161\/CIRCRESAHA.117.310355","article-title":"Calcium Signaling and Transcriptional Regulation in Cardiomyocytes","volume":"121","author":"Dewenter","year":"2017","journal-title":"Circ. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/nri3233","article-title":"Ion channels and transporters in lymphocyte function and immunity","volume":"12","author":"Feske","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0092-8674(00)81573-1","article-title":"A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy","volume":"93","author":"Molkentin","year":"1998","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"39370","DOI":"10.1074\/jbc.M603244200","article-title":"Myomaxin Is a Novel Transcriptional Target of MEF2A That Encodes a Xin-related \u03b1-Actinin-interacting Protein","volume":"281","author":"Huang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1161\/01.RES.87.12.e61","article-title":"Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles","volume":"87","author":"Yang","year":"2000","journal-title":"Circ. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1073\/pnas.0237225100","article-title":"Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy","volume":"100","author":"Vega","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1126\/science.aad3647","article-title":"Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression","volume":"351","author":"Li","year":"2016","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1681\/ASN.2018070729","article-title":"TRPC6 Binds to and Activates Calpain, Independent of Its Channel Activity, and Regulates Podocyte Cytoskeleton, Cell Adhesion, and Motility","volume":"30","author":"Farmer","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/nm1132","article-title":"Mice lacking calsarcin-1 are sensitized to calcineurin signaling and show accelerated cardiomyopathy in response to pathological biomechanical stress","volume":"10","author":"Frey","year":"2004","journal-title":"Nat. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1161\/CIRCULATIONAHA.107.711317","article-title":"Calsarcin-1 Protects Against Angiotensin-II\u2013Induced Cardiac Hypertrophy","volume":"116","author":"Frank","year":"2007","journal-title":"Circulation"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/5\/1092\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:24:03Z","timestamp":1760361843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/5\/1092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,28]]},"references-count":77,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["cells9051092"],"URL":"https:\/\/doi.org\/10.3390\/cells9051092","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,28]]}}}