{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:13:28Z","timestamp":1787375608684,"version":"build-2736575974"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"JSPS KAKEN","award":["25460292"],"award-info":[{"award-number":["25460292"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nitric oxide (NO) is produced from endothelial cells and cardiomyocytes composing the myocardium and benefits cardiac function through both vascular-dependent and\u2014independent effects. This study was purposed to investigate the possible adverse effect of NO focusing on the voltage-gated Na<jats:sup>+<\/jats:sup> channel in cardiomyocytes. We carried out patch-clamp experiments on rat neonatal cardiomyocytes demonstrating that NOC-18, an NO donor, significantly reduced Na<jats:sup>+<\/jats:sup> channel current in a dose-dependent manner by a long-term application for 24\u00a0h, accompanied by a reduction of Nav1.5-mRNA and the protein, and an increase of a transcription factor forkhead box protein O1 (FOXO1) in the nucleus. The effect of NOC-18 on the Na<jats:sup>+<\/jats:sup> channel was blocked by an inhibitor of thiol oxidation <jats:italic>N<\/jats:italic>-ethylmaleimide, a disulfide reducing agent disulfide 1,4-Dithioerythritol, or a FOXO1 activator paclitaxel, suggesting that NO is a negative regulator of the voltage-gated Na<jats:sup>+<\/jats:sup> channel through thiols in regulatory protein(s) for the channel transcription.<\/jats:p>","DOI":"10.1038\/s41598-021-90840-0","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T10:20:17Z","timestamp":1622197217000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nitric oxide down-regulates voltage-gated Na+ channel in cardiomyocytes possibly through S-nitrosylation-mediated signaling"],"prefix":"10.1038","volume":"11","author":[{"given":"Pu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenshi","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Kume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Morishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuki","family":"Kurokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsushige","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"90840_CR1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1093\/cvr\/cvq214","volume":"87","author":"J Tamargo","year":"2010","unstructured":"Tamargo, J., Caballero, R., G\u00f3mez, R. & Delp\u00f3n, E. Cardiac electrophysiological effects of nitric oxide. Cardiovasc. Res. 87, 593\u2013600 (2010).","journal-title":"Cardiovasc. Res."},{"key":"90840_CR2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.brainres.2018.12.027","volume":"1710","author":"K Sekiya","year":"2019","unstructured":"Sekiya, K. et al. Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased microglial cell numbers: Distinctive pathophysiological features from hypoxemia-induced brain damage. Brain Res. 1710, 22\u201332 (2019).","journal-title":"Brain Res."},{"key":"90840_CR3","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1111\/bph.12811","volume":"172","author":"I Andreadou","year":"2015","unstructured":"Andreadou, I. et al. The role of gasotransmitters NO, H2S and CO in myocardial ischaemia\/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. Br. J. Pharmacol. 172, 1587\u20131606 (2015).","journal-title":"Br. J. Pharmacol."},{"key":"90840_CR4","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/S0166-2236(02)02254-3","volume":"25","author":"GP Ahern","year":"2002","unstructured":"Ahern, G. P., Klyachko, V. A. & Jackson, M. B. cGMP and S-nitrosylation: two routes for modulation of neuronal excitability by NO. Trends Neurosci. 25, 510\u2013517 (2002).","journal-title":"Trends Neurosci."},{"key":"90840_CR5","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.niox.2007.09.086","volume":"18","author":"DR Gonz\u00e1lez","year":"2008","unstructured":"Gonz\u00e1lez, D. R. et al. Differential role of S-nitrosylation and the NO-cGMP-PKG pathway in cardiac contractility. Nitric Oxide 18, 157\u2013167 (2008).","journal-title":"Nitric Oxide"},{"key":"90840_CR6","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1097\/FJC.0b013e3181b72c9f","volume":"54","author":"DR Gonzalez","year":"2009","unstructured":"Gonzalez, D. R., Treuer, A., Sun, Q. A., Stamler, J. S. & Hare, J. M. S-Nitrosylation of cardiac ion channels. J. Cardiovasc. Pharmacol. 54, 188\u2013195 (2009).","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"90840_CR7","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.yjmcc.2014.01.003","volume":"73","author":"E Murphy","year":"2014","unstructured":"Murphy, E. et al. Signaling by S-nitrosylation in the heart. J. Mol. Cell. Cardiol. 73, 18\u201325 (2014).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"90840_CR8","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.3892\/mmr.2014.2968","volume":"11","author":"AV Treuer","year":"2015","unstructured":"Treuer, A. V. & Gonzalez, D. R. Nitric oxide synthases, S-nitrosylation and cardiovascular health: from molecular mechanisms to therapeutic opportunities. Mol. Med, Rep. 11, 1555\u20131565 (2015).","journal-title":"Mol. Med, Rep."},{"key":"90840_CR9","doi-asserted-by":"publisher","first-page":"4891","DOI":"10.1073\/pnas.0837428100","volume":"100","author":"SP Jones","year":"2003","unstructured":"Jones, S. P. et al. Endothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice. Proc. Natl. Acad. Sci. USA 100, 4891\u20134896 (2003).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"90840_CR10","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1089\/ars.2012.4824","volume":"18","author":"R Carnicer","year":"2013","unstructured":"Carnicer, R., Crabtree, M. J., Sivakumaran, V., Casadei, B. & Kass, D. A. Nitric oxide synthases in heart failure. Antioxid. Redox. Signal. 18, 1078\u20131099 (2013).","journal-title":"Antioxid. Redox. Signal."},{"key":"90840_CR11","doi-asserted-by":"publisher","first-page":"3633","DOI":"10.1161\/CIRCULATIONAHA.105.555623","volume":"112","author":"M Yano","year":"2005","unstructured":"Yano, M. et al. Correction of defective interdomain interaction within ryanodine receptor by antioxidant is a new therapeutic strategy against heart failure. Circulation 112, 3633\u20133643 (2005).","journal-title":"Circulation"},{"key":"90840_CR12","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s00210-005-1018-x","volume":"371","author":"C Lin","year":"2005","unstructured":"Lin, C. et al. Cross-talk between \u03b21-adrenoceptors and ETA receptors in modulation of the slow component of delayed rectifier K+ currents. Naunyn Schmiedebergs Arch Pharmacol. 371, 133\u2013140 (2005).","journal-title":"Naunyn Schmiedebergs Arch Pharmacol."},{"key":"90840_CR13","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s00018-016-2336-5","volume":"74","author":"T Fujita","year":"2017","unstructured":"Fujita, T., Umemura, M., Yokoyama, U., Okumura, S. & Ishikawa, Y. The role of Epac in the heart. Cell Mol Life Sci. 74, 591\u2013606 (2017).","journal-title":"Cell Mol Life Sci."},{"key":"90840_CR14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1089\/thy.2005.15.3","volume":"15","author":"M Sunagawa","year":"2005","unstructured":"Sunagawa, M. et al. Electrophysiologic characteristics of atrial myocytes in levo-thyroxine-treated rats. Thyroid 15, 3\u201311 (2005).","journal-title":"Thyroid"},{"key":"90840_CR15","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/j.1469-7793.1999.t01-1-00451.x","volume":"520","author":"AK Hammarstr\u00f6m","year":"1999","unstructured":"Hammarstr\u00f6m, A. K. & Gage, P. W. Nitric oxide increases persistent sodium current in rat hippocampal neurons. J. Physiol. 520, 451\u2013461 (1999).","journal-title":"J. Physiol."},{"key":"90840_CR16","doi-asserted-by":"publisher","first-page":"28810","DOI":"10.1074\/jbc.M003090200","volume":"275","author":"GP Ahern","year":"2000","unstructured":"Ahern, G. P., Hsu, S. F., Klyachko, V. A. & Jackson, M. B. Induction of persistent sodium current by exogenous and endogenous nitric oxide. J. Biol. Chem. 275, 28810\u201328815 (2000).","journal-title":"J. Biol. Chem."},{"key":"90840_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0022-510X(96)00102-5","volume":"141","author":"S Shibuta","year":"1996","unstructured":"Shibuta, S., Mashimo, T., Zhang, P., Ohara, A. & Yoshiya, I. A new nitric oxide donor, NOC-18, exhibits a nociceptive effect in the rat formalin model. J. Neurol. Sci. 141, 1\u20135 (1996).","journal-title":"J. Neurol. Sci."},{"key":"90840_CR18","doi-asserted-by":"publisher","first-page":"50949","DOI":"10.1074\/jbc.M308317200","volume":"278","author":"S Goldstein","year":"2003","unstructured":"Goldstein, S., Russo, A. & Samuni, A. Reactions of PTIO and carboxy-PTIO with \u2022NO, \u2022NO2, and O2-\u2022. J. Biol. Chem. 278, 50949\u201350955 (2003).","journal-title":"J. Biol. Chem."},{"key":"90840_CR19","doi-asserted-by":"publisher","first-page":"43P","DOI":"10.1042\/bj1100043P","volume":"110","author":"RJ Ellis","year":"1968","unstructured":"Ellis, R. J. The use of N-ethylmaleimide in stabilizing and measuring inorganic sulphur compounds. Biochem J. 110, 43P (1968).","journal-title":"Biochem J."},{"key":"90840_CR20","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/S0960-0760(03)00074-8","volume":"84","author":"S Lo","year":"2003","unstructured":"Lo, S. et al. Dithioerythritol (DTE) prevents inhibitory effects of triphenyltin (TPT) on the key enzymes of the human sex steroid hormone metabolism. J. Steroid Biochem. Mol. Biol. 84, 569\u2013576 (2003).","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"90840_CR21","doi-asserted-by":"publisher","first-page":"e32738","DOI":"10.1371\/journal.pone.0032738","volume":"7","author":"W Mao","year":"2012","unstructured":"Mao, W. et al. Reactive oxygen species suppress cardiac NaV15 expression through Foxo1. PLoS ONE 7, e32738 (2012).","journal-title":"PLoS ONE"},{"key":"90840_CR22","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1136\/heart.88.6.564","volume":"88","author":"JM Cotton","year":"2002","unstructured":"Cotton, J. M., Kearney, M. T. & Shah, A. M. Nitric oxide and myocardial function in heart failure: friend or foe?. Heart 88, 564\u2013566 (2002).","journal-title":"Heart"},{"key":"90840_CR23","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/BF00374390","volume":"423","author":"J Taniguchi","year":"1993","unstructured":"Taniguchi, J., Furukawa, K. I. & Shigekawa, M. Maxi K+ channels are stimulated by cyclic guanosine monophosphate-dependent protein kinase in canine coronary artery smooth muscle cells. Pflugers Arch. 423, 167\u2013172 (1993).","journal-title":"Pflugers Arch."},{"key":"90840_CR24","doi-asserted-by":"publisher","first-page":"22140","DOI":"10.1074\/jbc.M010103200","volume":"276","author":"J Han","year":"2001","unstructured":"Han, J., Kim, N., Kim, E., Ho, W. K. & Earm, Y. E. Modulation of ATP-sensitive potassium channels by cGMP-dependent protein kinase in rabbit ventricular myocytes. J. Biol. Chem. 276, 22140\u201322147 (2001).","journal-title":"J. Biol. Chem."},{"key":"90840_CR25","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1152\/jn.2000.83.1.198","volume":"83","author":"K Hirooka","year":"2000","unstructured":"Hirooka, K., Kourennyi, D. E. & Barnes, S. Calcium channel activation facilitated by nitric oxide in retinal ganglion cells. J. Neurophysiol. 83, 198\u2013206 (2000).","journal-title":"J. Neurophysiol."},{"key":"90840_CR26","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/S0168-0102(00)00236-4","volume":"39","author":"F Kawai","year":"2001","unstructured":"Kawai, F. & Miyachi, E. Modulation by cGMP of the voltage-gated currents in newt olfactory receptor cells. Neurosci. Res. 39, 327\u2013337 (2001).","journal-title":"Neurosci. Res."},{"key":"90840_CR27","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1161\/hh2301.100801","volume":"89","author":"GU Ahmmed","year":"2001","unstructured":"Ahmmed, G. U. et al. Nitric oxide modulates cardiac Na+ channel via protein kinase A and protein kinase G. Circ. Res. 89, 1005\u20131013 (2001).","journal-title":"Circ. Res."},{"key":"90840_CR28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0014-5793(97)01144-7","volume":"415","author":"JH Shin","year":"1997","unstructured":"Shin, J. H., Chung, S., Park, E. J., Uhm, D. Y. & Suh, C. K. Nitric oxide directly activates calcium-activated potassium channels from rat brain reconstituted into planar lipid bilayer. FEBS Lett. 415, 299\u2013302 (1997).","journal-title":"FEBS Lett."},{"key":"90840_CR29","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1085\/jgp.108.4.277","volume":"108","author":"DL Campbell","year":"1996","unstructured":"Campbell, D. L., Stamler, J. S. & Strauss, H. C. Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols. J. Gen. Physiol. 108, 277\u2013293 (1996).","journal-title":"J. Gen. Physiol."},{"key":"90840_CR30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/S0896-6273(00)80055-0","volume":"16","author":"MC Broillet","year":"1996","unstructured":"Broillet, M. C. & Firestein, S. Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds. Neuron 16, 377\u2013385 (1996).","journal-title":"Neuron"},{"key":"90840_CR31","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.yjmcc.2013.03.013","volume":"61","author":"J Cheng","year":"2013","unstructured":"Cheng, J. et al. Caveolin-3 suppresses late sodium current by inhibiting nNOS-dependent S-nitrosylation of SCN5A. J. Mol. Cell Cardiol. 61, 102\u2013110 (2013).","journal-title":"J. Mol. Cell Cardiol."},{"key":"90840_CR32","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1046\/j.1471-4159.2000.0751455.x","volume":"75","author":"A Bal-Price","year":"2000","unstructured":"Bal-Price, A. & Brown, G. C. Nitric-oxide-induced necrosis and apoptosis in PC12 cells mediated by mitochondria. J. Neurochem. 75, 1455\u20131464 (2000).","journal-title":"J. Neurochem."},{"key":"90840_CR33","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1164\/ajrccm.162.2.9907039","volume":"162","author":"I Okamoto","year":"2000","unstructured":"Okamoto, I. et al. Evaluating the role of inducible nitric oxide synthase using a novel and selective inducible nitric oxide synthase inhibitor in septic lung injury produced by cecal ligation and puncture. Am. J. Respir. Crit. Care Med. 162, 716\u2013722 (2000).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"90840_CR34","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S0003-4975(96)00770-9","volume":"63","author":"N Barzaghi","year":"1997","unstructured":"Barzaghi, N. et al. ECMO and inhaled nitric oxide for cardiopulmonary failure after heart retransplantation. Ann. Thorac. Surg. 63, 533\u2013535 (1997).","journal-title":"Ann. Thorac. Surg."},{"key":"90840_CR35","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1152\/jn.00440.2017","volume":"120","author":"M Ikeda","year":"2018","unstructured":"Ikeda, M. & Yoshino, M. Nitric oxide augments single persistent Na+ channel currents via the cGMP\/PKG signaling pathway in Kenyon cells isolated from cricket mushroom bodies. J. Neurophysiol. 120, 720\u2013728 (2018).","journal-title":"J. Neurophysiol."},{"key":"90840_CR36","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/978-1-60327-029-8_3","volume":"610","author":"E Nagababu","year":"2010","unstructured":"Nagababu, E. & Rifkind, J. M. Measurement of plasma nitrite by chemiluminescence. Methods Mol Biol. 610, 41\u201349 (2010).","journal-title":"Methods Mol Biol."},{"key":"90840_CR37","first-page":"1256","volume":"255","author":"EA Kowaluk","year":"1990","unstructured":"Kowaluk, E. A. & Fung, H. L. Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J. Pharmacol. Exp. Ther. 255, 1256\u20131264 (1990).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"90840_CR38","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3389\/fpls.2013.00293","volume":"4","author":"A Mengel","year":"2013","unstructured":"Mengel, A., Chaki, M., Shekariesfahlan, A. & Lindermayr, C. Effect of nitric oxide on gene transcription\u2014S-nitrosylation of nuclear proteins. Front. Plant Sci. 4, 293 (2013).","journal-title":"Front. Plant Sci."},{"key":"90840_CR39","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1093\/jxb\/erj053","volume":"57","author":"S Gr\u00fcn","year":"2006","unstructured":"Gr\u00fcn, S., Lindermayr, C., Sell, S. & Durner, J. Nitric oxide and gene regulation in plants. J. Exp. Bot. 57, 507\u2013516 (2006).","journal-title":"J. Exp. Bot."},{"key":"90840_CR40","doi-asserted-by":"publisher","first-page":"C977","DOI":"10.1152\/ajpcell.00027.2012","volume":"303","author":"TN Schachter","year":"2012","unstructured":"Schachter, T. N., Shen, T., Liu, Y. & Schneider, M. F. Kinetics of nuclear-cytoplasmic translocation of Foxo1 and Foxo3A in adult skeletal muscle fibers. Am. J. Physiol. Cell Physiol. 303, C977-990 (2012).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"90840_CR41","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1161\/01.RES.0000088351.58510.21","volume":"93","author":"PB Massion","year":"2003","unstructured":"Massion, P. B., Feron, O., Dessy, C. & Balligand, J. L. Nitric oxide and cardiac function: ten years after, and continuing. Circ. Res. 93, 388\u2013398 (2003).","journal-title":"Circ. Res."},{"key":"90840_CR42","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/S0163-7258(99)00072-8","volume":"86","author":"AM Shah","year":"2000","unstructured":"Shah, A. M. & MacCarthy, P. A. Paracrine and autocrine effects of nitric oxide on myocardial function. Pharmacol. Ther. 86, 49\u201386 (2000).","journal-title":"Pharmacol. Ther."},{"key":"90840_CR43","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1161\/01.CIR.97.2.161","volume":"97","author":"JM Hare","year":"1998","unstructured":"Hare, J. M., Givertz, M. M., Creager, M. A. & Colucci, W. S. Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure: potentiation of \u03b2-adrenergic inotropic responsiveness. Circulation 97, 161\u2013166 (1998).","journal-title":"Circulation"},{"key":"90840_CR44","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1253\/jcj.60.779","volume":"60","author":"K Ishikawa","year":"1996","unstructured":"Ishikawa, K. et al. Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prev. Group. Jpn Circ J. 60, 779\u2013788 (1996).","journal-title":"Secondary Prev. Group. Jpn Circ J."},{"key":"90840_CR45","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1253\/circj.71.301","volume":"71","author":"S Kojima","year":"2007","unstructured":"Kojima, S. et al. Long-term nitrate therapy after acute myocardial infarction does not improve or aggravate prognosis. Circ. J. 71, 301\u2013307 (2007).","journal-title":"Circ. J."},{"key":"90840_CR46","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1016\/j.mayocp.2018.11.032","volume":"94","author":"T Tsujimoto","year":"2019","unstructured":"Tsujimoto, T. & Kajio, H. Use of nitrates and risk of cardiovascular events in patients with heart failure with preserved ejection fraction. Mayo Clin Proc. 94, 1210\u20131220 (2019).","journal-title":"Mayo Clin Proc."},{"key":"90840_CR47","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.yjmcc.2007.03.905","volume":"42","author":"Y Wang","year":"2007","unstructured":"Wang, Y. et al. Transcription factors Csx\/Nkx25 and GATA4 distinctly regulate expression of Ca2+ channels in neonatal rat heart. J. Mol. Cell Cardiol. 42, 1045\u20131053 (2007).","journal-title":"J. Mol. Cell Cardiol."},{"key":"90840_CR48","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1111\/j.1476-5381.2009.00174.x","volume":"157","author":"L Kang","year":"2009","unstructured":"Kang, L. et al. Bepridil up-regulates cardiac Na+ channels as a long-term effect by blunting proteasome signals through inhibition of calmodulin activity. Br. J. Pharmacol. 157, 404\u2013414 (2009).","journal-title":"Br. J. Pharmacol."},{"key":"90840_CR49","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1007\/s12576-017-0590-4","volume":"68","author":"K Masuda","year":"2018","unstructured":"Masuda, K. et al. Testosterone-mediated upregulation of delayed rectifier potassium channel in cardiomyocytes causes abbreviation of QT intervals in rats. J. Physiol. Sci. 68, 759\u2013767 (2018).","journal-title":"J. Physiol. Sci."},{"key":"90840_CR50","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1253\/circj.CJ-20-0288","volume":"84","author":"Y Wang","year":"2020","unstructured":"Wang, Y. et al. Binge alcohol exposure triggers atrial fibrillation through T-type Ca2+ channel upregulation via protein kinase C (PKC)\/glycogen synthesis kinase 3\u03b2 (GSK3\u03b2)\/nuclear factor of activated T-cells (NFAT) signaling\u2014an experimental account of holiday heart syndrome. Circ. J. 84, 1931\u20131940 (2020).","journal-title":"Circ. J."},{"key":"90840_CR51","doi-asserted-by":"publisher","first-page":"e0201891","DOI":"10.1371\/journal.pone.0201891","volume":"13","author":"M Morishima","year":"2018","unstructured":"Morishima, M., Horikawa, K. & Funaki, M. Cardiomyocytes cultured on mechanically compliant substrates, but not on conventional culture devices, exhibit prominent mitochondrial dysfunction due to reactive oxygen species and insulin resistance under high glucose. PLoS ONE 13, e0201891 (2018).","journal-title":"PLoS ONE"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90840-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90840-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90840-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T08:49:45Z","timestamp":1670057385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90840-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["90840"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-90840-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,28]]},"assertion":[{"value":"26 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11273"}}