{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:06Z","timestamp":1787028546154,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnolog\u00eda de Argentina (ANCPyT)","doi-asserted-by":"publisher","award":["PICT 2020#2427"],"award-info":[{"award-number":["PICT 2020#2427"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnolog\u00eda de Argentina (ANCPyT)","doi-asserted-by":"publisher","award":["PIP1781"],"award-info":[{"award-number":["PIP1781"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","award":["PICT 2020#2427"],"award-info":[{"award-number":["PICT 2020#2427"]}]},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","award":["PIP1781"],"award-info":[{"award-number":["PIP1781"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The G-protein-coupled estrogen receptor (GPER) has been described to exert several cardioprotective effects. However, the exact mechanism involved in cardiac protection remains unclear. The aim of this study is to investigate the role of GPER activation on excitation\u2013contraction coupling (ECC) and the possibility that such effect participates in cardioprotection. The cardiac myocytes of male Wistar rats were isolated with a digestive buffer and loaded with Fura-2-AM for the measurement of intracellular calcium transient (CaT). Sarcomere shortening (SS) and L-type calcium current (ICaL) were also registered. The confocal technique was used to measure nitric oxide (NO) production in cells loaded with DAF-FM-diacetate. Cardiac myocytes exposed to 17-\u03b2-estradiol (E2, 10 nM) or G-1 (1 \u03bcM) for fifteen minutes decreased CaT, SS, and ICaL. These effects were prevented using G-36 (antagonist of GPER, 1 \u03bcM), L-Name (NO synthase -NOS- inhibitor, 100 nM), or wortmannin (phosphoinositide-3-kinase -PI3K- inhibitor, 100 nM). Moreover, G1 increased NO production, and this effect was abolished in the presence of wortmannin. We concluded that the selective activation of GPER with E2 or G1 in the isolated cardiac myocytes of male rats induced a negative inotropic effect due to the reduction in ICaL and the decrease in CaT. Finally, the pathway that we proposed to be implicated in these effects is PI3K-NOS-NO.<\/jats:p>","DOI":"10.3390\/ijms25168993","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T10:11:28Z","timestamp":1724062288000},"page":"8993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Activation of G Protein-Coupled Estrogen Receptor (GPER) Negatively Modulates Cardiac Excitation\u2013Contraction Coupling (ECC) through the PI3K\/NOS\/NO Pathway"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2346-9544","authenticated-orcid":false,"given":"Leandro A.","family":"Diaz-Zegarra","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares \u201cDr. Horacio E. Cingolani\u201d, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata\u2014CONICET, La Plata 1900, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda S.","family":"Espejo","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares \u201cDr. Horacio E. Cingolani\u201d, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata\u2014CONICET, La Plata 1900, Buenos Aires, Argentina"},{"name":"Biomedicine Department, Health, Aarhus University, 8000 Aarhus, Midtjylland, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro M.","family":"Iba\u00f1ez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares \u201cDr. Horacio E. Cingolani\u201d, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata\u2014CONICET, La Plata 1900, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica E.","family":"Rando","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares \u201cDr. Horacio E. Cingolani\u201d, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata\u2014CONICET, La Plata 1900, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-412X","authenticated-orcid":false,"given":"Lucia E.","family":"Pagola","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares \u201cDr. Horacio E. Cingolani\u201d, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata\u2014CONICET, La Plata 1900, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica C.","family":"De Giusti","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares \u201cDr. Horacio E. Cingolani\u201d, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata\u2014CONICET, La Plata 1900, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto A.","family":"Aiello","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares \u201cDr. Horacio E. Cingolani\u201d, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata\u2014CONICET, La Plata 1900, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0014-5793(97)00278-0","article-title":"A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid tissue","volume":"407","author":"Kvingedal","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1006\/geno.1997.4972","article-title":"Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer","volume":"45","author":"Carmeci","year":"1997","journal-title":"Genomics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nchembio775","article-title":"Virtual and biomolecular screening converge on a selective agonist for GPR30","volume":"2","author":"Bologa","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1124\/pr.114.009712","article-title":"International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators","volume":"67","author":"Prossnitz","year":"2015","journal-title":"Pharmacol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jsbmb.2017.03.021","article-title":"Twenty years of the G protein-coupled estrogen receptor GPER: Historical and personal perspectives","volume":"176","author":"Barton","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129433","DOI":"10.1172\/JCI129433","article-title":"17beta-Estradiol and estrogen receptor alpha protect right ventricular function in pulmonary hypertension via BMPR2 and apelin","volume":"131","author":"Frump","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.yjmcc.2019.06.007","article-title":"Mechanism of 17beta-estradiol stimulated integration of human mesenchymal stem cells in heart tissue","volume":"133","author":"Mihai","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_8","first-page":"3","article-title":"A new membrane G protein-coupled receptor (GPR30) is involved in the cardiac effects of 17beta-estradiol in the male rat","volume":"60","author":"Filice","year":"2009","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1159\/000354252","article-title":"The G protein-coupled estrogen receptor 1 (GPER1\/GPR30) agonist G-1 regulates vascular smooth muscle cell Ca2+ handling","volume":"50","author":"Holm","year":"2013","journal-title":"J. Vasc. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"H1806","DOI":"10.1152\/ajpheart.00283.2009","article-title":"Activation of a novel estrogen receptor, GPER, is cardioprotective in male and female rats","volume":"297","author":"Deschamps","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E882","DOI":"10.1152\/ajpendo.00037.2011","article-title":"Activation of G protein-coupled estrogen receptor induces endothelium-independent relaxation of coronary artery smooth muscle","volume":"301","author":"Yu","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E398","DOI":"10.1152\/ajpendo.00534.2013","article-title":"G protein-coupled estrogen receptor 1 mediates relaxation of coronary arteries via cAMP\/PKA-dependent activation of MLCP","volume":"307","author":"Yu","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.steroids.2013.10.017","article-title":"Vasodilation by GPER in mesenteric arteries involves both endothelial nitric oxide and smooth muscle cAMP signaling","volume":"81","author":"Lindsey","year":"2014","journal-title":"Steroids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.yjmcc.2015.10.024","article-title":"Aldosterone stimulates the cardiac sodium\/bicarbonate cotransporter via activation of the g protein-coupled receptor gpr30","volume":"89","author":"Orlowski","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1210\/en.2008-1664","article-title":"Chronic treatment with the G protein-coupled receptor 30 agonist G-1 decreases blood pressure in ovariectomized mRen2.Lewis rats","volume":"150","author":"Lindsey","year":"2009","journal-title":"Endocrinology"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jessup, J.A., Lindsey, S.H., Wang, H., Chappell, M.C., and Groban, L. (2010). Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015433"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/cvr\/cvs090","article-title":"Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats","volume":"94","author":"Wang","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kang, S., Liu, Y., Sun, D., Zhou, C., Liu, A., Xu, C., Hao, Y., Li, D., Yan, C., and Sun, H. (2012). Chronic activation of the G protein-coupled receptor 30 with agonist G-1 attenuates heart failure. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048185"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.surg.2010.03.011","article-title":"Signaling via GPR30 protects the myocardium from ischemia\/reperfusion injury","volume":"148","author":"Weil","year":"2010","journal-title":"Surgery"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kabir, M.E., Singh, H., Lu, R., Olde, B., Leeb-Lundberg, L.M., and Bopassa, J.C. (2015). G Protein-Coupled Estrogen Receptor 1 Mediates Acute Estrogen-Induced Cardioprotection via MEK\/ERK\/GSK-3beta Pathway after Ischemia\/Reperfusion. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135988"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4329","DOI":"10.1111\/bph.14033","article-title":"Activation of G protein-coupled oestrogen receptor 1 at the onset of reperfusion protects the myocardium against ischemia\/reperfusion injury by reducing mitochondrial dysfunction and mitophagy","volume":"174","author":"Feng","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ibanez, A.M., Gonzalez Arbelaez, L.F., Ciocci Pardo, A., Mosca, S., Lofeudo, J.M., Velez Rueda, J.O., Aiello, E.A., and De Giusti, V.C. (2022). Chronic GPER activation prevents ischemia\/reperfusion injury in ovariectomized rats. Biochim. Biophys. Acta Gen. Subj., 1866.","DOI":"10.1016\/j.bbagen.2021.130060"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1006\/jmcc.1994.1118","article-title":"Chronic administration of nicardipine attenuates myocardial stunning in isolated rabbit hearts","volume":"26","author":"Moreyra","year":"1994","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1097\/00005344-199602000-00010","article-title":"Chronic nifedipine treatment diminishes cardiac inotropic response to nifedifine: Functional upregulation of dihydropyridine receptors","volume":"27","author":"Mosca","year":"1996","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pardo, A.C., Diaz Zegarra, L.A., Gonzalez Arbelaez, L.F., Ibanez, A.M., Diaz, R.G., Aiello, E.A., and Mosca, S.M. (2022). Cardioprotective effects of N-methylacetazolamide mediated by inhibition of L-type Ca(2+) channel current. Biochim. Biophys. Acta Gen. Subj., 1866.","DOI":"10.1016\/j.bbagen.2022.130098"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/cvr\/cvt021","article-title":"L-type calcium channel targeting and local signalling in cardiac myocytes","volume":"98","author":"Shaw","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1161\/01.RES.87.12.1095","article-title":"Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C","volume":"87","author":"Kamp","year":"2000","journal-title":"Circ. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1083\/jcb.129.3.673","article-title":"Immunolocalization of sarcolemmal dihydropyridine receptor and sarcoplasmic reticular triadin and ryanodine receptor in rabbit ventricle and atrium","volume":"129","author":"Carl","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.yjmcc.2022.08.001","article-title":"Elucidating the role of the L-type calcium channel in excitability and energetics in the heart: The ISHR 2020 Research Achievement Award Lecture","volume":"172","author":"Hool","year":"2022","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1006\/jmcc.1998.0755","article-title":"L-type calcium channel abundance and function with cardiac hypertrophy and failure: A review","volume":"30","author":"Mukherjee","year":"1998","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0039-128X(96)00014-1","article-title":"Modulation of hypertensive heart disease by estrogen","volume":"61","author":"Grohe","year":"1996","journal-title":"Steroids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1113\/expphysiol.1998.sp004115","article-title":"Rapid modulation of L-type calcium current by acutely applied oestrogens in isolated cardiac myocytes from human, guinea-pig and rat","volume":"83","author":"Meyer","year":"1998","journal-title":"Exp. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"H1031","DOI":"10.1152\/ajpheart.00249.2017","article-title":"Effect of ovariectomy on intracellular Ca2+ regulation in guinea pig cardiomyocytes","volume":"313","author":"Yang","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"H2421","DOI":"10.1152\/ajpheart.01225.2007","article-title":"Genomic deletion of estrogen receptors ERalpha and ERbeta does not alter estrogen-mediated inhibition of Ca2+ influx and contraction in murine cardiomyocytes","volume":"294","author":"Ullrich","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Whitcomb, V., Wauson, E., Christian, D., Clayton, S., Giles, J., and Tran, Q.K. (2020). Regulation of beta adrenoceptor-mediated myocardial contraction and calcium dynamics by the G protein-coupled estrogen receptor 1. Biochem. Pharmacol., 171.","DOI":"10.1016\/j.bcp.2019.113727"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1080\/19336950.2016.1195533","article-title":"The cardiac electrogenic sodium\/bicarbonate cotransporter (NBCe1) is activated by aldosterone through the G protein-coupled receptor 30 (GPR 30)","volume":"10","author":"Orlowski","year":"2016","journal-title":"Channels"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rocca, C., Femmino, S., Aquila, G., Granieri, M.C., De Francesco, E.M., Pasqua, T., Rigiracciolo, D.C., Fortini, F., Cerra, M.C., and Maggiolini, M. (2018). Notch1 Mediates Preconditioning Protection Induced by GPER in Normotensive and Hypertensive Female Rat Hearts. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00521"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"28063","DOI":"10.1074\/jbc.M704893200","article-title":"Atrial glutathione content, calcium current, and contractility","volume":"282","author":"Carnes","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1161\/01.RES.0000202707.79018.0a","article-title":"Hypercontractile female hearts exhibit increased S-nitrosylation of the L-type Ca2+ channel alpha1 subunit and reduced ischemia\/reperfusion injury","volume":"98","author":"Sun","year":"2006","journal-title":"Circ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ceca.2015.06.004","article-title":"Modulation of L-type Ca2+ channel activity by neuronal nitric oxide synthase and myofilament Ca2+ sensitivity in cardiac myocytes from hypertensive rat","volume":"58","author":"Wang","year":"2015","journal-title":"Cell Calcium"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1161\/01.RES.0000259042.04576.6a","article-title":"Conditional neuronal nitric oxide synthase overexpression impairs myocardial contractility","volume":"100","author":"Burkard","year":"2007","journal-title":"Circ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1097\/FJC.0b013e3181b72c9f","article-title":"S-Nitrosylation of cardiac ion channels","volume":"54","author":"Gonzalez","year":"2009","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Francis, A.J., Firth, J.M., Sanchez-Alonso, J.L., Gorelik, J., and MacLeod, K.T. (2022). GPER limits adverse changes to Ca2+ signalling and arrhythmogenic activity in ovariectomised guinea pig cardiomyocytes. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.1023755"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev.pharmtox.48.113006.094646","article-title":"G protein-coupled receptor sorting to endosomes and lysosomes","volume":"48","author":"Marchese","year":"2008","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nature08910","article-title":"The endocytic matrix","volume":"463","author":"Scita","year":"2010","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.mce.2010.07.010","article-title":"Regulation of GPCR signal networks via membrane trafficking","volume":"331","author":"Hanyaloglu","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1007\/s11010-021-04219-w","article-title":"Role of PI3K\/Akt signaling pathway in cardiac fibrosis","volume":"476","author":"Qin","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1469-7793.1998.137bf.x","article-title":"Evidence for an electrogenic Na+-HCO3\u2212 symport in rat cardiac myocytes","volume":"512","author":"Aiello","year":"1998","journal-title":"J. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s00424-017-2058-z","article-title":"The reduced myofilament responsiveness to calcium contributes to the negative force-frequency relationship in rat cardiomyocytes: Role of reactive oxygen species and p-38 map kinase","volume":"469","author":"Espejo","year":"2017","journal-title":"Pflugers Arch."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:38:47Z","timestamp":1760110727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,19]]},"references-count":49,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168993"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168993","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,19]]}}}