{"id":"https://openalex.org/W4398166145","doi":"https://doi.org/10.1152/physiol.2024.39.s1.1397","title":"In Cardiac Myocytes the SGLT2 Inhibitor Ertugliflozin Attenuates Cytosolic Ca2+ Peaks After Adrenergic Stimulation","display_name":"In Cardiac Myocytes the SGLT2 Inhibitor Ertugliflozin Attenuates Cytosolic Ca2+ Peaks After Adrenergic Stimulation","publication_year":2024,"publication_date":"2024-05-01","ids":{"openalex":"https://openalex.org/W4398166145","doi":"https://doi.org/10.1152/physiol.2024.39.s1.1397"},"language":"en","primary_location":{"id":"doi:10.1152/physiol.2024.39.s1.1397","doi":"https://doi.org/10.1152/physiol.2024.39.s1.1397","is_oa":false,"landing_page_url":"https://doi.org/10.1152/physiol.2024.39.s1.1397","pdf_url":null,"source":{"id":"https://openalex.org/S88977973","display_name":"Physiology","issn_l":"0886-1714","issn":["0886-1714","1522-161X","1548-9213","1548-9221"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320155","host_organization_name":"American Physiological Society","host_organization_lineage":["https://openalex.org/P4310320155"],"host_organization_lineage_names":["American Physiological Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Physiology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5020771192","display_name":"Mihir Dixit","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mihir Dixit","raw_affiliation_strings":["University of California, San Diego, San Diego, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California, San Diego, San Diego, CA, United States","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040163590","display_name":"Sifat Alam","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]},{"id":"https://openalex.org/I4210099595","display_name":"VA San Diego Healthcare System","ror":"https://ror.org/00znqwq11","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1322918889","https://openalex.org/I2799886695","https://openalex.org/I4210099595","https://openalex.org/I4210138663"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sifat Alam","raw_affiliation_strings":["VA San Diego Healthcare System, University of California, San Diego, San Diego, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"VA San Diego Healthcare System, University of California, San Diego, San Diego, CA, United States","institution_ids":["https://openalex.org/I36258959","https://openalex.org/I4210099595"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101003537","display_name":"Tengteng Zhao","orcid":"https://orcid.org/0009-0007-1247-574X","observed_orcids":["https://orcid.org/0009-0007-1247-574X"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Tengteng Zhao","raw_affiliation_strings":["University of California, San Diego, San Diego, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California, San Diego, San Diego, CA, United States","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Quoc Nguyen","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]},{"id":"https://openalex.org/I4210099595","display_name":"VA San Diego Healthcare System","ror":"https://ror.org/00znqwq11","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1322918889","https://openalex.org/I2799886695","https://openalex.org/I4210099595","https://openalex.org/I4210138663"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Quoc Nguyen","raw_affiliation_strings":["VA San Diego Healthcare System, and University of California, San Diego, San Diego, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"VA San Diego Healthcare System, and University of California, San Diego, San Diego, CA, United States","institution_ids":["https://openalex.org/I36258959","https://openalex.org/I4210099595"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071356717","display_name":"Kyle Gierden","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]},{"id":"https://openalex.org/I4210099595","display_name":"VA San Diego Healthcare System","ror":"https://ror.org/00znqwq11","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1322918889","https://openalex.org/I2799886695","https://openalex.org/I4210099595","https://openalex.org/I4210138663"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kyle Gierden","raw_affiliation_strings":["VA San Diego Healthcare System, and University of California, San Diego, San Diego, CA, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"VA San Diego Healthcare System, and University of California, San Diego, San Diego, CA, United States","institution_ids":["https://openalex.org/I36258959","https://openalex.org/I4210099595"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108752705","display_name":"Jason X.\u2010J. Yuan","orcid":"https://orcid.org/0000-0002-0685-4862","observed_orcids":["https://orcid.org/0000-0002-0685-4862"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jason Yuan","raw_affiliation_strings":["University of California San Diego, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5085734264","display_name":"Volker Vallon","orcid":"https://orcid.org/0000-0002-9211-2063","observed_orcids":["https://orcid.org/0000-0002-9211-2063"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Volker Vallon","raw_affiliation_strings":["University of California San Diego, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0962712,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"39","issue":"S1","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10401","display_name":"Diabetes Treatment and Management","score":0.5663999915122986,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10401","display_name":"Diabetes Treatment and Management","score":0.5663999915122986,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10217","display_name":"Cardiac electrophysiology and arrhythmias","score":0.30000001192092896,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10821","display_name":"Cardiovascular Function and Risk Factors","score":0.02590000070631504,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ertugliflozin","display_name":"ertugliflozin","score":0.996999979019165},{"id":"https://openalex.org/keywords/sglt2-inhibitors","display_name":"SGLT2 inhibitors","score":0.9760000109672546},{"id":"https://openalex.org/keywords/cardiomyocytes","display_name":"cardiomyocytes","score":0.6499999761581421},{"id":"https://openalex.org/keywords/intracellular-calcium","display_name":"intracellular calcium","score":0.9049999713897705},{"id":"https://openalex.org/keywords/calcium-homeostasis","display_name":"calcium homeostasis","score":0.9049999713897705},{"id":"https://openalex.org/keywords/adrenergic-stimulation","display_name":"adrenergic stimulation","score":0.890999972820282},{"id":"https://openalex.org/keywords/phenylephrine","display_name":"phenylephrine","score":0.9340000152587891},{"id":"https://openalex.org/keywords/nhe1-inhibition","display_name":"NHE1 inhibition","score":0.7699999809265137},{"id":"https://openalex.org/keywords/cariporide","display_name":"cariporide","score":0.996999979019165},{"id":"https://openalex.org/keywords/phospholamban","display_name":"phospholamban","score":0.7699999809265137},{"id":"https://openalex.org/keywords/heart-failure","display_name":"heart failure","score":0.7919999957084656},{"id":"https://openalex.org/keywords/type-2-diabetes","display_name":"type 2 diabetes","score":0.9089999794960022},{"id":"https://openalex.org/keywords/cardiomyocyte-contraction","display_name":"cardiomyocyte contraction","score":0.8040000200271606}],"concepts":[{"id":"https://openalex.org/C98539663","wikidata":"https://www.wikidata.org/wiki/Q220599","display_name":"Cytosol","level":3,"score":0.6971818208694458},{"id":"https://openalex.org/C24998067","wikidata":"https://www.wikidata.org/wiki/Q4114622","display_name":"Stimulation","level":2,"score":0.6947839856147766},{"id":"https://openalex.org/C207200792","wikidata":"https://www.wikidata.org/wiki/Q428914","display_name":"Myocyte","level":2,"score":0.6849830746650696},{"id":"https://openalex.org/C158453852","wikidata":"https://www.wikidata.org/wiki/Q4684738","display_name":"Adrenergic","level":3,"score":0.5499529242515564},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.5329011082649231},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5191882848739624},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4756562113761902},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.3474203646183014},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3342992663383484},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.30015289783477783},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2302647829055786},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.20458468794822693},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.14782491326332092},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.11069267988204956}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1152/physiol.2024.39.s1.1397","doi":"https://doi.org/10.1152/physiol.2024.39.s1.1397","is_oa":false,"landing_page_url":"https://doi.org/10.1152/physiol.2024.39.s1.1397","pdf_url":null,"source":{"id":"https://openalex.org/S88977973","display_name":"Physiology","issn_l":"0886-1714","issn":["0886-1714","1522-161X","1548-9213","1548-9221"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320155","host_organization_name":"American Physiological Society","host_organization_lineage":["https://openalex.org/P4310320155"],"host_organization_lineage_names":["American Physiological Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Physiology","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":1.0,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4225320030","https://openalex.org/W4414936589","https://openalex.org/W4400038346","https://openalex.org/W4393986100","https://openalex.org/W4318682925","https://openalex.org/W3099073074","https://openalex.org/W2772835527","https://openalex.org/W3204973181","https://openalex.org/W2901156727","https://openalex.org/W4378717402"],"abstract_inverted_index":{"A":[0],"novel":[1],"class":[2],"of":[3,207,221,263,275,289],"antidiabetic":[4],"drugs,":[5],"called":[6],"gliflozins,":[7],"inhibit":[8],"sodium-glucose":[9],"cotransporter":[10],"2":[11,22],"(SGLT2i)":[12],"to":[13,174,191,235,285,295],"lower":[14],"blood":[15],"glucose":[16],"levels":[17,126,206,279],"in":[18,33,57,74,247,335,354],"patients":[19,35],"with":[20,36,92,121,131,183],"Type":[21],"diabetes":[23],"(T2DM).":[24],"Gliflozins":[25],"reduce":[26],"mortality":[27],"and":[28,62,97,108,136,145,161,193,195,214,270,331],"heart":[29],"failure":[30],"(HF)":[31],"hospitalizations":[32],"HF":[34],"or":[37,110,152,343],"without":[38],"T2DM,":[39],"but":[40,170,240],"the":[41,64,100,236,241,286,297,320,325,355],"molecular":[42,298],"mechanisms":[43,299],"are":[44,55,273,293,339],"unclear.":[45],"We":[46],"hypothesize":[47],"that":[48,63,254],"modulating":[49],"effects":[50],"on":[51,258,303],"cardiac":[52,249,304],"calcium":[53,71,125,268,271,305],"homeostasis":[54,260],"involved":[56,353],"SGLT2i-induced":[58],"benefits":[59],"during":[60],"HF,":[61,276],"SGLT2i":[65,237],"ertugliflozin":[66],"(ERTU)":[67],"will":[68],"alter":[69],"cytosolic":[70,124],"concentration":[72],"([Ca2+]cyt)":[73,127],"contracting":[75,248],"cardiomyocytes":[76],"after":[77,168,200,230,280],"adrenergic":[78],"stimulation.":[79],"Cardiomyocytes":[80],"were":[81,117],"isolated":[82,147],"from":[83],"0\u20132-day":[84],"old":[85],"C57BL/6J":[86],"mice,":[87],"treated":[88],"for":[89,139,148,155,347],"72":[90,114],"hours":[91],"either":[93,118],"ERTU":[94,107,164,173,231,238],"(100":[95],"nM,":[96],"1":[98,162],"\u03bcM),":[99,106,135],"NHE-1":[101,242],"inhibitor":[102,243],"cariporide":[103],"(CARI,":[104],"10":[105],"CARI,":[109],"vehicle":[111,192],"(Ctrl).":[112],"After":[113],"hours,":[115],"cells":[116,129],"A)":[119],"loaded":[120],"Fura-2,":[122],"baseline":[123,188],"recorded,":[128],"stimulated":[130],"phenylephrine":[132],"(PE,":[133],"100":[134,159,171],"[Ca2+]cyt":[137,166,186,198,246,259,278],"recorded":[138],"additional":[140,341,344],"30":[141],"minutes,":[142],"B)":[143],"lysed":[144],"protein":[146,205],"analysis":[149],"by":[150,311],"immunoblotting,":[151],"C)":[153],"fixed":[154],"immunohistochemical":[156],"assessment.":[157],"Results:":[158],"nM":[160,172],"uM":[163],"reduced":[165,277],"peaks":[167,199],"PE,":[169],"a":[175],"lesser":[176],"degree.":[177],"In":[178],"contrast,":[179],"72-hour-long":[180],"NHE1":[181,264],"inhibition":[182],"CARI":[184,244],"increased":[185,204,245],"at":[187,324],"when":[189],"compared":[190],"ERTU,":[194],"further":[196],"enhanced":[197],"PE.":[201],"Immunoblotting":[202],"revealed":[203,225],"S16":[208],"phosphorylated":[209],"phospholamban,":[210,213],"decreased":[211],"total":[212],"upregulated":[215],"sarcomeric":[216,222,227],"\u03b1-actinin":[217,223],"post-ERTU.":[218],"Immunohistochemical":[219],"assessment":[220],"localization":[224],"improved":[226],"Z-line":[228],"organization":[229],"administration.":[232],"Sustained":[233],"exposure":[234],"reduced,":[239],"myocytes.":[250],"These":[251],"data":[252],"indicate":[253],"ERTU\u2019s":[255,301],"beneficial":[256],"effect":[257,288],"is":[261,319,332],"independent":[262],"inhibition.":[265],"Since":[266],"disturbed":[267],"handling":[269],"overload":[272],"hallmarks":[274],"sympathetic":[281],"stimulation":[282],"may":[283],"contribute":[284],"cardioprotective":[287],"SGLT2i.":[290],"Further":[291],"studies":[292],"needed":[294],"unravel":[296],"behind":[300],"influence":[302],"homeostasis.":[306],"This":[307,318],"study":[308],"was":[309,351],"funded":[310],"Merck":[312],"&":[313],"Co.,":[314],"Inc.":[315],"(Kenilworth,":[316],"NJ).":[317],"full":[321],"abstract":[322],"presented":[323],"American":[326],"Physiology":[327,350],"Summit":[328],"2024":[329],"meeting":[330],"only":[333],"available":[334,346],"HTML":[336],"format.":[337],"There":[338],"no":[340],"versions":[342],"content":[345],"this":[348],"abstract.":[349],"not":[352],"peer":[356],"review":[357],"process.":[358]},"counts_by_year":[],"updated_date":"2026-09-27T08:07:27.782135","created_date":"2024-05-22T00:00:00"}