{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:16:56Z","timestamp":1788585416622,"version":"build-2803163510"},"reference-count":115,"publisher":"Japanese Society of Veterinary Science","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Vet. Med. Sci.","The Journal of Veterinary Medical Science"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1292\/jvms.26-0186","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:10:02Z","timestamp":1783635002000},"page":"1407-1418","source":"Crossref","is-referenced-by-count":0,"title":["The Na&lt;sup&gt;+&lt;\/sup&gt;\/Ca&lt;sup&gt;2+&lt;\/sup&gt; exchanger: molecular structure, functional          regulation, and mode-selective modulation"],"prefix":"10.1292","volume":"88","author":[{"given":"Naoshige","family":"ONO","sequence":"first","affiliation":[{"name":"Laboratory of Prophylactic Pharmacology, Osaka Metropolitan University              Graduate School of Veterinary Science, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"NISHIYAMA","sequence":"additional","affiliation":[{"name":"Laboratory of Prophylactic Pharmacology, Osaka Metropolitan University              Graduate School of Veterinary Science, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasu-Taka","family":"AZUMA","sequence":"additional","affiliation":[{"name":"Laboratory of Prophylactic Pharmacology, Osaka Metropolitan University              Graduate School of Veterinary Science, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"122","reference":[{"key":"1","unstructured":"1. Alberts              B, Johnson              A, Lewis              J, Raff              M, Roberts              K, Walter              P. 2002.          Signaling through G-Protein-Linked Cell-Surface Receptors. In: Molecular Biology of the          Cell. 4th ed., Garland Science, New York."},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Amran              MS, Homma              N, Hashimoto              K. 2003.            Pharmacology of KB-R7943: a Na+-Ca2+ exchange inhibitor.              <i>Cardiovasc Drug Rev<\/i>          21: 255\u2013276.","DOI":"10.1111\/j.1527-3466.2003.tb00121.x"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Bagur              R, Hajn\u00f3czky              G. 2017.            Intracellular Ca<sup>2+<\/sup> sensing: its role in calcium homeostasis            and signaling. <i>Mol Cell<\/i>          66: 780\u2013788.","DOI":"10.1016\/j.molcel.2017.05.028"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Berridge              MJ. 2001.            The versatility and complexity of calcium signalling.              <i>Novartis Found Symp<\/i>          239: 52\u201364, discussion 64\u201367, 150\u2013159.","DOI":"10.1002\/0470846674.ch6"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Berridge              MJ. 2002.            The endoplasmic reticulum: a multifunctional signaling            organelle. <i>Cell Calcium<\/i>          32: 235\u2013249.","DOI":"10.1016\/S0143416002001823"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Bers              DM, Bassani              JW, Bassani              RA. 1996.            Na-Ca exchange and Ca fluxes during contraction and relaxation in            mammalian ventricular muscle. <i>Ann N Y Acad            Sci<\/i>          779: 430\u2013442.","DOI":"10.1111\/j.1749-6632.1996.tb44818.x"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Bezprozvanny              I. 2005.            The inositol 1,4,5-trisphosphate receptors.              <i>Cell Calcium<\/i>          38: 261\u2013272.","DOI":"10.1016\/j.ceca.2005.06.030"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Bkaily              G, Jacques              D. 2023.            Calcium homeostasis, transporters, and blockers in health and diseases of            the cardiovascular system. <i>Int J Mol            Sci<\/i>          24: 8803.","DOI":"10.3390\/ijms24108803"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Blaustein              MP, Lederer              WJ. 1999.            Sodium\/calcium exchange: its physiological implications.              <i>Physiol Rev<\/i>          79: 763\u2013854.","DOI":"10.1152\/physrev.1999.79.3.763"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Bootman              MD, Berridge              MJ. 1995.            The elemental principles of calcium signaling.              <i>Cell<\/i>          83: 675\u2013678.","DOI":"10.1016\/0092-8674(95)90179-5"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Bootman              MD, Berridge              MJ, Roderick              HL. 2002.            Calcium signalling: more messengers, more channels, more            complexity. <i>Curr Biol<\/i>          12: R563\u2013R565.","DOI":"10.1016\/S0960-9822(02)01055-2"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Bourne              HR, Nicoll              R. 1993.            Molecular machines integrate coincident synaptic signals.              <i>Cell<\/i>          72 Suppl: 65\u201375.","DOI":"10.1016\/S0092-8674(05)80029-7"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Breder              J, Sabelhaus              CF, Opitz              T, Reymann              KG, Schr\u00f6der              UH. 2000.            Inhibition of different pathways influencing Na(+) homeostasis protects            organotypic hippocampal slice cultures from hypoxic\/hypoglycemic injury.              <i>Neuropharmacology<\/i>          39: 1779\u20131787.","DOI":"10.1016\/S0028-3908(00)00027-7"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Brini              M, Carafoli              E. 2011.            The plasma membrane Ca<sup>2<\/sup>+ ATPase and the plasma membrane sodium            calcium exchanger cooperate in the regulation of cell calcium.              <i>Cold Spring Harb Perspect Biol<\/i>          3: a004168.","DOI":"10.1101\/cshperspect.a004168"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Carafoli              E. 1987.            Intracellular calcium homeostasis. <i>Annu              Rev Biochem<\/i>          56: 395\u2013433.","DOI":"10.1146\/annurev.bi.56.070187.002143"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Carafoli              E. 1994.            Biogenesis: plasma membrane calcium ATPase: 15 years of work on the            purified enzyme. <i>FASEB J<\/i>          8: 993\u20131002.","DOI":"10.1096\/fasebj.8.13.7926378"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Carafoli              E. 1992.            The Ca2+ pump of the plasma membrane. <i>J              Biol Chem<\/i>          267: 2115\u20132118.","DOI":"10.1016\/S0021-9258(18)45848-6"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Carafoli              E. 2005.            Calcium\u2014a universal carrier of biological signals. Delivered on 3 July            2003 at the Special FEBS Meeting in Brussels. <i>FEBS              J<\/i>          272: 1073\u20131089.","DOI":"10.1111\/j.1742-4658.2005.04546.x"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Chou              AC, Ju              YT, Pan              CY. 2015.            Calmodulin interacts with the sodium\/calcium exchanger NCX1 to regulate            activity. <i>PLoS One<\/i>          10: e0138856.","DOI":"10.1371\/journal.pone.0138856"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Christel              C, Lee              A. 2012.            Ca2+-dependent modulation of voltage-gated Ca2+ channels.              <i>Biochim Biophys Acta<\/i>          1820: 1243\u20131252.","DOI":"10.1016\/j.bbagen.2011.12.012"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Clapham              DE. 2007.            Calcium signaling. <i>Cell<\/i>          131: 1047\u20131058.","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Cooper              DM, Mons              N, Karpen              JW. 1995.            Adenylyl cyclases and the interaction between calcium and cAMP            signalling. <i>Nature<\/i>          374: 421\u2013424.","DOI":"10.1038\/374421a0"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Dhyani              V, Gare              S, Gupta              RK, Swain              S, Venkatesh              KV, Giri              L. 2020.            GPCR mediated control of calcium dynamics: A systems            perspective. <i>Cell Signal<\/i>          74: 109717.","DOI":"10.1016\/j.cellsig.2020.109717"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Dong              Y, Yu              Z, Li              Y, Huang              B, Bai              Q, Gao              Y, Chen              Q, Li              N, He              L, Zhao              Y. 2024.            Structural insight into the allosteric inhibition of human sodium-calcium            exchanger NCX1 by XIP and SEA0400. <i>EMBO            J<\/i>          43: 14\u201331.","DOI":"10.1038\/s44318-023-00013-0"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Fill              M, Copello              JA. 2002.            Ryanodine receptor calcium release channels.              <i>Physiol Rev<\/i>          82: 893\u2013922.","DOI":"10.1152\/physrev.00013.2002"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Formisano              L, Guida              N, Mascolo              L, Serani              A, Laudati              G, Pizzorusso              V, Annunziato              L. 2020.            Transcriptional and epigenetic regulation of ncx1 and ncx3 in the            brain. <i>Cell Calcium<\/i>          87: 102194.","DOI":"10.1016\/j.ceca.2020.102194"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Foskett              JK, White              C, Cheung              KH, Mak              DOD. 2007.            Inositol trisphosphate receptor Ca2+ release channels.              <i>Physiol Rev<\/i>          87: 593\u2013658.","DOI":"10.1152\/physrev.00035.2006"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Furuichi              T, Furutama              D, Hakamata              Y, Nakai              J, Takeshima              H, Mikoshiba              K. 1994.            Multiple types of ryanodine receptor\/Ca2+ release channels are            differentially expressed in rabbit brain. <i>J              Neurosci<\/i>          14: 4794\u20134805.","DOI":"10.1523\/JNEUROSCI.14-08-04794.1994"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Geramipour              A, Kohajda              Z, Corici              C, Prorok              J, Szakonyi              Z, Oravecz              K, M\u00e1rton              Z, Nagy              N, T\u00f3th              A, Acsai              K, Vir\u00e1g              L, Varr\u00f3              A, Jost              N. 2016.            The investigation of the cellular electrophysiological and antiarrhythmic            effects of a novel selective sodium-calcium exchanger inhibitor, GYKB-6635, in canine            and guinea-pig hearts. <i>Can J Physiol            Pharmacol<\/i>          94: 1090\u20131101.","DOI":"10.1139\/cjpp-2015-0566"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Giladi              M, Boyman              L, Mikhasenko              H, Hiller              R,                Khananshvili              D. 2010.            Essential role of the CBD1-CBD2 linker in slow dissociation of Ca2+ from            the regulatory two-domain tandem of NCX1. <i>J Biol              Chem<\/i>          285: 28117\u201328125.","DOI":"10.1074\/jbc.M110.127001"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Giladi              M, Hiller              R, Hirsch              JA,                Khananshvili              D. 2013.            Population shift underlies Ca2+-induced regulatory transitions in the            sodium-calcium exchanger (NCX). <i>J Biol            Chem<\/i>          288: 23141\u201323149.","DOI":"10.1074\/jbc.M113.471698"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Giladi              M, Sasson              Y, Fang              X, Hiller              R, Buki              T, Wang              YX, Hirsch              JA,                Khananshvili              D. 2012.            A common Ca2+-driven interdomain module governs eukaryotic NCX            regulation. <i>PLoS One<\/i>          7: e39985.","DOI":"10.1371\/journal.pone.0039985"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Giladi              M, Tal              I,                Khananshvili              D. 2016.            Structural features of ion transport and allosteric regulation in            sodium-calcium exchanger (NCX) proteins. <i>Front              Physiol<\/i>          7: 30.","DOI":"10.3389\/fphys.2016.00030"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. Giorgi              C, Danese              A, Missiroli              S, Patergnani              S, Pinton              P. 2018.            Calcium dynamics as a machine for decoding signals.              <i>Trends Cell Biol<\/i>          28: 258\u2013273.","DOI":"10.1016\/j.tcb.2018.01.002"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Gomez-Ospina              N, Tsuruta              F,                Barreto-Chang              O, Hu              L, Dolmetsch              R. 2006.            The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2            encodes a transcription factor. <i>Cell<\/i>          127: 591\u2013606.","DOI":"10.1016\/j.cell.2006.10.017"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Guerini              D, Coletto              L, Carafoli              E. 2005.            Exporting calcium from cells. <i>Cell              Calcium<\/i>          38: 281\u2013289.","DOI":"10.1016\/j.ceca.2005.06.032"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. Hasegawa              H, Muraoka              M, Matsui              K, Kojima              A. 2003.            Discovery of a novel potent Na+\/Ca2+ exchanger inhibitor: design,            synthesis and structure-activity relationships of 3,4-dihydro-2(1H)-quinazolinone            derivatives. <i>Bioorg Med Chem Lett<\/i>          13: 3471\u20133475.","DOI":"10.1016\/S0960-894X(03)00744-3"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. He              S, Ruknudin              A, Bambrick              LL, Lederer              WJ, Schulze              DH. 1998.            Isoform-specific regulation of the Na+\/Ca2+ exchanger in rat astrocytes            and neurons by PKA. <i>J Neurosci<\/i>          18: 4833\u20134841.","DOI":"10.1523\/JNEUROSCI.18-13-04833.1998"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Hertle              DN, Yeckel              MF. 2007.            Distribution of inositol-1,4,5-trisphosphate receptor isotypes and            ryanodine receptor isotypes during maturation of the rat hippocampus.              <i>Neuroscience<\/i>          150: 625\u2013638.","DOI":"10.1016\/j.neuroscience.2007.09.058"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40. Hewavitharana              T, Deng              X, Soboloff              J, Gill              DL. 2007.            Role of STIM and Orai proteins in the store-operated calcium signaling            pathway. <i>Cell Calcium<\/i>          42: 173\u2013182.","DOI":"10.1016\/j.ceca.2007.03.009"},{"key":"41","unstructured":"41. Hille              B. Ion Channels of Excitable          Membranes, 4th ed., Oxford University Press, Oxford."},{"key":"42","doi-asserted-by":"crossref","unstructured":"42. Iwamoto              T, Kita              S, Uehara              A, Inoue              Y, Taniguchi              Y, Imanaga              I, Shigekawa              M. 2001.            Structural domains influencing sensitivity to isothiourea derivative            inhibitor KB-R7943 in cardiac Nna+\/Ca2+ exchanger. <i>Mol              Pharmacol<\/i>          59: 524\u2013531.","DOI":"10.1016\/S0026-895X(24)12244-4"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43. Iwamoto              T, Watano              T, Shigekawa              M. 1996.            A novel isothiourea derivative selectively inhibits the reverse mode of            Na+\/Ca2+ exchange in cells expressing NCX1. <i>J Biol              Chem<\/i>          271: 22391\u201322397.","DOI":"10.1074\/jbc.271.37.22391"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44. Iwamoto              T. 2005.            Sodium-calcium exchange inhibitors: therapeutic potential in            cardiovascular diseases. <i>Future            Cardiol<\/i>          1: 519\u2013529.","DOI":"10.2217\/14796678.1.4.519"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45. Iwamoto              T. 2004.            Forefront of Na+\/Ca2+ exchanger studies: molecular pharmacology of            Na+\/Ca2+ exchange inhibitors. <i>J Pharmacol            Sci<\/i>          96: 27\u201332.","DOI":"10.1254\/jphs.FMJ04002X6"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46. Iwamoto              T. 2007.            Na+\/Ca2+ exchange as a drug target\u2014insights from molecular pharmacology            and genetic engineering. <i>Ann N Y Acad            Sci<\/i>          1099: 516\u2013528.","DOI":"10.1196\/annals.1387.039"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47. Iwamoto              T, Inoue              Y, Ito              K, Sakaue              T, Kita              S, Katsuragi              T. 2004.            The exchanger inhibitory peptide region-dependent inhibition of Na+\/Ca2+            exchange by SN-6 [2-[4-(4-nitrobenzyloxy)benzyl]thiazolidine-4-carboxylic acid ethyl            ester], a novel benzyloxyphenyl derivative. <i>Mol              Pharmacol<\/i>          66: 45\u201355.","DOI":"10.1124\/mol.66.1.45"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48. Iwamoto              T, Kita              S. 2006.            YM-244769, a novel Na+\/Ca2+ exchange inhibitor that preferentially            inhibits NCX3, efficiently protects against hypoxia\/reoxygenation-induced SH-SY5Y            neuronal cell damage. <i>Mol Pharmacol<\/i>          70: 2075\u20132083.","DOI":"10.1124\/mol.106.028464"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49. Iwamoto              T, Kita              S, Uehara              A, Imanaga              I, Matsuda              T, Baba              A, Katsuragi              T. 2004.            Molecular determinants of Na+\/Ca2+ exchange (NCX1) inhibition by            SEA0400. <i>J Biol Chem<\/i>          279: 7544\u20137553.","DOI":"10.1074\/jbc.M310491200"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50. Jain              A, Woolley              CS. 2023.            Mechanisms that underlie expression of estradiol-induced excitatory            synaptic potentiation in the hippocampus differ between males and            females. <i>J Neurosci<\/i>          43: 1298\u20131309.","DOI":"10.1523\/JNEUROSCI.2080-19.2023"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51. James              G, Butt              AM. 2002.            P2Y and P2X purinoceptor mediated Ca2+ signalling in glial cell pathology            in the central nervous system. <i>Eur J            Pharmacol<\/i>          447: 247\u2013260.","DOI":"10.1016\/S0014-2999(02)01756-9"},{"key":"52","doi-asserted-by":"crossref","unstructured":"52. Jeffs              GJ, Meloni              BP, Bakker              AJ, Knuckey              NW. 2007.            The role of the Na+\/Ca2+ exchanger (NCX) in neurons following            ischaemia. <i>J Clin Neurosci<\/i>          14: 507\u2013514.","DOI":"10.1016\/j.jocn.2006.07.013"},{"key":"53","unstructured":"53. John HB, Heidelberger R, Neal MW From Molecules to          Networks. https:\/\/www.sciencedirect.com\/book\/edited-volume\/9780123971791\/from-molecules-to-networks          [accessed on April 7, 2026]."},{"key":"54","doi-asserted-by":"crossref","unstructured":"54. Jost              N, Nagy              N, Corici              C, Kohajda              Z, Horv\u00e1th              A, Acsai              K, Biliczki              P, Levijoki              J, Pollesello              P,                Koskelainen              T, Otsomaa              L, T\u00f3th              A, Papp              JG, Varr\u00f3              A, Vir\u00e1g              L. 2013.            ORM-10103, a novel specific inhibitor of the Na+\/Ca2+ exchanger,            decreases early and delayed afterdepolarizations in the canine heart.              <i>Br J Pharmacol<\/i>          170: 768\u2013778.","DOI":"10.1111\/bph.12228"},{"key":"55","doi-asserted-by":"crossref","unstructured":"55. Kamato              D, Thach              L, Bernard              R, Chan              V, Zheng              W, Kaur              H, Brimble              M, Osman              N, Little              PJ. 2015.            Structure, function, pharmacology, and therapeutic potential of the G            protein, G\u03b1\/q,11. <i>Front Cardiovasc Med<\/i>          2: 14.","DOI":"10.3389\/fcvm.2015.00014"},{"key":"56","doi-asserted-by":"crossref","unstructured":"56. Khananshvili              D. 2014.            Sodium-calcium exchangers (NCX): molecular hallmarks underlying the            tissue-specific and systemic functions. <i>Pflugers              Arch<\/i>          466: 43\u201360.","DOI":"10.1007\/s00424-013-1405-y"},{"key":"57","doi-asserted-by":"crossref","unstructured":"57. Khananshvili              D. 2020.            Basic and editing mechanisms underlying ion transport and regulation in            NCX variants. <i>Cell Calcium<\/i>          85: 102131.","DOI":"10.1016\/j.ceca.2019.102131"},{"key":"58","doi-asserted-by":"crossref","unstructured":"58. Kofuji              P, Lederer              WJ, Schulze              DH. 1994.            Mutually exclusive and cassette exons underlie alternatively spliced            isoforms of the Na\/Ca exchanger. <i>J Biol            Chem<\/i>          269: 5145\u20135149.","DOI":"10.1016\/S0021-9258(17)37667-6"},{"key":"59","doi-asserted-by":"crossref","unstructured":"59. Kohajda              Z,                Farkas-Morvay              N, Jost              N, Nagy              N, Geramipour              A, Horv\u00e1th              A, Varga              RS, Hornyik              T, Corici              C, Acsai              K, Horv\u00e1th              B, Prorok              J, \u00d6rd\u00f6g              B, D\u00e9ri              S, T\u00f3th              D, Levijoki              J, Pollesello              P,                Koskelainen              T, Otsomaa              L, T\u00f3th              A, Baczk\u00f3              I, Lepr\u00e1n              I, N\u00e1n\u00e1si              PP, Papp              JG, Varr\u00f3              A, Vir\u00e1g              L. 2016.            The effect of a novel highly selective inhibitor of the sodium\/calcium            exchanger (NCX) on cardiac arrhythmias in in vitro and in vivo            experiments. <i>PLoS One<\/i>          11: e0166041.","DOI":"10.1371\/journal.pone.0166041"},{"key":"60","doi-asserted-by":"crossref","unstructured":"60. Kouba              S, Hague              F, Ahidouch              A,                Ouadid-Ahidouch              H. 2022.            Crosstalk between Ca<sup>2+<\/sup> Signaling and Cancer Stemness: The Link            to Cisplatin Resistance. <i>Int J Mol Sci<\/i>          23: 10687.","DOI":"10.3390\/ijms231810687"},{"key":"61","doi-asserted-by":"crossref","unstructured":"61. Kozak              JA, Putney              JW. 2018. Calcium          Entry Channels in Non-Excitable Cells, CRC Press\/Taylor &amp; Francis, Boca          Raton.","DOI":"10.1201\/9781315152592"},{"key":"62","doi-asserted-by":"crossref","unstructured":"62. Lewis              RS. 2007.            The molecular choreography of a store-operated calcium            channel. <i>Nature<\/i>          446: 284\u2013287.","DOI":"10.1038\/nature05637"},{"key":"63","doi-asserted-by":"crossref","unstructured":"63. Li              S, Jiang              Q, Stys              PK. 2000.            Important role of reverse Na(+)-Ca(2+) exchange in spinal cord white            matter injury at physiological temperature. <i>J              Neurophysiol<\/i>          84: 1116\u20131119.","DOI":"10.1152\/jn.2000.84.2.1116"},{"key":"64","doi-asserted-by":"crossref","unstructured":"64. Liao              J, Li              H, Zeng              W, Sauer              DB, Belmares              R, Jiang              Y. 2012.            Structural insight into the ion-exchange mechanism of the sodium\/calcium            exchanger. <i>Science<\/i>          335: 686\u2013690.","DOI":"10.1126\/science.1215759"},{"key":"65","doi-asserted-by":"crossref","unstructured":"65. Liao              J, Marinelli              F, Lee              C, Huang              Y,                Faraldo-G\u00f3mez              JD, Jiang              Y. 2016.            Mechanism of extracellular ion exchange and binding-site occlusion in a            sodium\/calcium exchanger. <i>Nat Struct Mol            Biol<\/i>          23: 590\u2013599.","DOI":"10.1038\/nsmb.3230"},{"key":"66","doi-asserted-by":"crossref","unstructured":"66. Linck              B, Qiu              Z, He              Z, Tong              Q, Hilgemann              DW, Philipson              KD. 1998.            Functional comparison of the three isoforms of the Na+\/Ca2+ exchanger            (NCX1, NCX2, NCX3). <i>Am J Physiol<\/i>          274: C415\u2013C423.","DOI":"10.1152\/ajpcell.1998.274.2.C415"},{"key":"67","doi-asserted-by":"crossref","unstructured":"67. Little              PJ, Neylon              CB, Tkachuk              VA, Bobik              A. 1992.            Endothelin-1 and endothelin-3 stimulate calcium mobilization by different            mechanisms in vascular smooth muscle. <i>Biochem Biophys              Res Commun<\/i>          183: 694\u2013700.","DOI":"10.1016\/0006-291X(92)90538-V"},{"key":"68","doi-asserted-by":"crossref","unstructured":"68. Luo              J, Wang              Y, Chen              X, Chen              H, Kintner              DB, Shull              GE, Philipson              KD, Sun              D. 2007.            Increased tolerance to ischemic neuronal damage by knockdown of Na+-Ca2+            exchanger isoform 1. <i>Ann N Y Acad Sci<\/i>          1099: 292\u2013305.","DOI":"10.1196\/annals.1387.016"},{"key":"69","doi-asserted-by":"crossref","unstructured":"69. MacGregor              DG,                Avshalumov              MV, Rice              ME. 2003.            Brain edema induced by in vitro ischemia: causal factors and            neuroprotection. <i>J Neurochem<\/i>          85: 1402\u20131411.","DOI":"10.1046\/j.1471-4159.2003.01772.x"},{"key":"70","doi-asserted-by":"crossref","unstructured":"70. Mackrill              JJ. 2010.            Ryanodine receptor calcium channels and their partners as drug            targets. <i>Biochem Pharmacol<\/i>          79: 1535\u20131543.","DOI":"10.1016\/j.bcp.2010.01.014"},{"key":"71","doi-asserted-by":"crossref","unstructured":"71. Magee              WP, Deshmukh              G, Deninno              MP, Sutt              JC, Chapman              JG, Tracey              WR. 2003.            Differing cardioprotective efficacy of the Na+\/Ca2+ exchanger inhibitors            SEA0400 and KB-R7943. <i>Am J Physiol Heart Circ              Physiol<\/i>          284: H903\u2013H910.","DOI":"10.1152\/ajpheart.00784.2002"},{"key":"72","doi-asserted-by":"crossref","unstructured":"72. Marinelli              F, Almagor              L, Hiller              R, Giladi              M,                Khananshvili              D,                Faraldo-G\u00f3mez              JD. 2014.            Sodium recognition by the Na+\/Ca2+ exchanger in the outward-facing            conformation. <i>Proc Natl Acad Sci USA<\/i>          111: E5354\u2013E5362.","DOI":"10.1073\/pnas.1415751111"},{"key":"73","doi-asserted-by":"crossref","unstructured":"73. Martin-Romero              FJ,                Pascual-Caro              C,                Lopez-Guerrero              A,                Espinosa-Bermejo              N,                Pozo-Guisado              E,                Martin-Romero              FJ,                Pascual-Caro              C,                Lopez-Guerrero              A,                Espinosa-Bermejo              N,                Pozo-Guisado              E. 2018.          Regulation of Calcium Signaling by STIM1 and ORAI1. In: Calcium and Signal Transduction,          IntechOpen.","DOI":"10.5772\/intechopen.78587"},{"key":"74","doi-asserted-by":"crossref","unstructured":"74. Martonosi              AN. 1984.            Mechanisms of Ca2+ release from sarcoplasmic reticulum of skeletal            muscle. <i>Physiol Rev<\/i>          64: 1240\u20131320.","DOI":"10.1152\/physrev.1984.64.4.1240"},{"key":"75","doi-asserted-by":"crossref","unstructured":"75. Matsuda              T, Arakawa              N, Takuma              K, Kishida              Y, Kawasaki              Y, Sakaue              M, Takahashi              K, Takahashi              T, Suzuki              T, Ota              T,                Hamano-Takahashi              A, Onishi              M, Tanaka              Y, Kameo              K, Baba              A. 2001.            SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger,            attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic            models. <i>J Pharmacol Exp Ther<\/i>          298: 249\u2013256.","DOI":"10.1016\/S0022-3565(24)29375-7"},{"key":"76","doi-asserted-by":"crossref","unstructured":"76. Matsuoka              S, Nicoll              DA, Reilly              RF, Hilgemann              DW, Philipson              KD. 1993.            Initial localization of regulatory regions of the cardiac sarcolemmal            Na(+)-Ca2+ exchanger. <i>Proc Natl Acad Sci            USA<\/i>          90: 3870\u20133874.","DOI":"10.1073\/pnas.90.9.3870"},{"key":"77","unstructured":"77. Michel              LYM,                Hoenderop              JGJ, Bindels              RJM. 2015.            Towards understanding the role of the Na<sup>2+<\/sup>-Ca<sup>2+<\/sup>            exchanger isoform 3. <i>Rev Physiol Biochem              Pharmacol<\/i>          168: 31\u201357."},{"key":"78","doi-asserted-by":"crossref","unstructured":"78. Michel              LYM, Verkaart              S, Koopman              WJH, Willems              PHGM,                Hoenderop              JGJ, Bindels              RJM. 2014.            Function and regulation of the Na+-Ca2+ exchanger NCX3 splice variants in            brain and skeletal muscle. <i>J Biol Chem<\/i>          289: 11293\u201311303.","DOI":"10.1074\/jbc.M113.529388"},{"key":"79","doi-asserted-by":"crossref","unstructured":"79. Miller              RJ. 1991.            The control of neuronal Ca2+ homeostasis.              <i>Prog Neurobiol<\/i>          37: 255\u2013285.","DOI":"10.1016\/0301-0082(91)90028-Y"},{"key":"80","doi-asserted-by":"crossref","unstructured":"80. Molinaro              P, Cantile              M, Cuomo              O, Secondo              A,                Pannaccione              A, Ambrosino              P, Pignataro              G, Fiorino              F, Severino              B, Gatta              E, Sisalli              MJ, Milanese              M, Scorziello              A, Bonanno              G, Robello              M, Santagada              V, Caliendo              G, Di Renzo              G, Annunziato              L. 2013.            Neurounina-1, a novel compound that increases Na+\/Ca2+ exchanger            activity, effectively protects against stroke damage.              <i>Mol Pharmacol<\/i>          83: 142\u2013156.","DOI":"10.1124\/mol.112.080986"},{"key":"81","doi-asserted-by":"crossref","unstructured":"81. Neer              EJ. 1994.            G proteins: critical control points for transmembrane            signals. <i>Protein Sci<\/i>          3: 3\u201314.","DOI":"10.1002\/pro.5560030102"},{"key":"82","doi-asserted-by":"crossref","unstructured":"82. Neer              EJ. 1995.            Heterotrimeric G proteins: organizers of transmembrane            signals. <i>Cell<\/i>          80: 249\u2013257.","DOI":"10.1016\/0092-8674(95)90407-7"},{"key":"83","doi-asserted-by":"crossref","unstructured":"83. Nilius              B, Owsianik              G. 2011.            The transient receptor potential family of ion channels.              <i>Genome Biol<\/i>          12: 218.","DOI":"10.1186\/gb-2011-12-3-218"},{"key":"84","doi-asserted-by":"crossref","unstructured":"84. Niu              CF, Watanabe              Y, Ono              K, Iwamoto              T, Yamashita              K, Satoh              H, Urushida              T, Hayashi              H, Kimura              J. 2007.            Characterization of SN-6, a novel Na+\/Ca2+ exchange inhibitor in guinea            pig cardiac ventricular myocytes. <i>Eur J              Pharmacol<\/i>          573: 161\u2013169.","DOI":"10.1016\/j.ejphar.2007.06.033"},{"key":"85","doi-asserted-by":"crossref","unstructured":"85. Ogata              M, Iwamoto              T, Tazawa              N, Nishikawa              M, Yamashita              J, Takaoka              M, Matsumura              Y. 2003.            A novel and selective Na+\/Ca2+ exchange inhibitor, SEA0400, improves            ischemia\/reperfusion-induced renal injury. <i>Eur J              Pharmacol<\/i>          478: 187\u2013198.","DOI":"10.1016\/j.ejphar.2003.08.082"},{"key":"86","doi-asserted-by":"crossref","unstructured":"86. Oravecz              K, Kormos              A, Gruber              A, M\u00e1rton              Z, Kohajda              Z, Mirzaei              L, Jost              N, Levijoki              J, Pollesello              P,                Koskelainen              T, Otsomaa              L, T\u00f3th              A, Papp              JG, N\u00e1n\u00e1si              PP, Antoons              G, Varr\u00f3              A, Acsai              K, Nagy              N. 2018.            Inotropic effect of NCX inhibition depends on the relative activity of            the reverse NCX assessed by a novel inhibitor ORM-10962 on canine ventricular            myocytes. <i>Eur J Pharmacol<\/i>          818: 278\u2013286.","DOI":"10.1016\/j.ejphar.2017.10.039"},{"key":"87","doi-asserted-by":"crossref","unstructured":"87. Otsomaa              L, Levijoki              J, Wohlfahrt              G, Chapman              H, Koivisto              AP, Syrj\u00e4nen              K,                Koskelainen              T, Peltokorpi              SE,                Finckenberg              P, Heikkil\u00e4              A, Abi-Gerges              N, Ghetti              A, Miller              PE, Page              G, Mervaala              E, Nagy              N, Kohajda              Z, Jost              N, Vir\u00e1g              L, Varr\u00f3              A, Papp              JG. 2020.            Discovery and characterization of ORM-11372, a novel inhibitor of the            sodium-calcium exchanger with positive inotropic activity.              <i>Br J Pharmacol<\/i>          177: 5534\u20135554.","DOI":"10.1111\/bph.15257"},{"key":"88","doi-asserted-by":"crossref","unstructured":"88. Ottolia              M, John              S, Hazan              A, Goldhaber              JI. 2021.            The cardiac Na<sup>+<\/sup> -Ca<sup>2+<\/sup> exchanger: from structure to            function. <i>Compr Physiol<\/i>          12: 2681\u20132717.","DOI":"10.1002\/j.2040-4603.2022.tb00196.x"},{"key":"89","doi-asserted-by":"crossref","unstructured":"89. Pchitskaya              E, Popugaeva              E,                Bezprozvanny              I. 2018.            Calcium signaling and molecular mechanisms underlying neurodegenerative            diseases. <i>Cell Calcium<\/i>          70: 87\u201394.","DOI":"10.1016\/j.ceca.2017.06.008"},{"key":"90","doi-asserted-by":"crossref","unstructured":"90. Pelat              M, Barbe              F, Daveu              C, Ly-Nguyen              L, Lartigue              T, Marque              S, Tavares              G, Ballet              V, Guillon              JM,                Steinmeyer              K, Wirth              K, G\u00f6gelein              H, Arndt              P, Rackelmann              N, Weston              J,                Bellevergue              P, McCort              G, Trellu              M, Lucats              L, Beauverger              P,                Pruniaux-Harnist              MP, Janiak              P,                Ch\u00e9zalviel-Guilbert              F. 2021.            SAR340835, a novel selective Na<sup>+<\/sup>\/Ca<sup>2+<\/sup> exchanger            inhibitor, improves cardiac function and restores sympathovagal balance in heart            failure. <i>J Pharmacol Exp Ther<\/i>          377: 293\u2013304.","DOI":"10.1124\/jpet.120.000238"},{"key":"91","doi-asserted-by":"crossref","unstructured":"91. Philipson              KD, Nicoll              DA. 2000.            Sodium-calcium exchange: a molecular perspective.              <i>Annu Rev Physiol<\/i>          62: 111\u2013133.","DOI":"10.1146\/annurev.physiol.62.1.111"},{"key":"92","doi-asserted-by":"crossref","unstructured":"92. Prakriya              M. 2009.            The molecular physiology of CRAC channels.              <i>Immunol Rev<\/i>          231: 88\u201398.","DOI":"10.1111\/j.1600-065X.2009.00820.x"},{"key":"93","doi-asserted-by":"crossref","unstructured":"93. Primeau              JO, Armanious              GP, Fisher              ME, Young              HS. 2018.            The SarcoEndoplasmic reticulum calcium ATPase.              <i>Subcell Biochem<\/i>          87: 229\u2013258.","DOI":"10.1007\/978-981-10-7757-9_8"},{"key":"94","doi-asserted-by":"crossref","unstructured":"94. Quednau              BD, Nicoll              DA, Philipson              KD. 1997.            Tissue specificity and alternative splicing of the Na+\/Ca2+ exchanger            isoforms NCX1, NCX2, and NCX3 in rat. <i>Am J              Physiol<\/i>          272: C1250\u2013C1261.","DOI":"10.1152\/ajpcell.1997.272.4.C1250"},{"key":"95","doi-asserted-by":"crossref","unstructured":"95. Ren              X, Philipson              KD. 2013.            The topology of the cardiac Na<sup>+<\/sup>\/Ca<sup>2+<\/sup> exchanger,            NCX1. <i>J Mol Cell Cardiol<\/i>          57: 68\u201371.","DOI":"10.1016\/j.yjmcc.2013.01.010"},{"key":"96","doi-asserted-by":"crossref","unstructured":"96. Roderick              HL, Berridge              MJ, Bootman              MD. 2003.            Calcium-induced calcium release. <i>Curr              Biol<\/i>          13: R425.","DOI":"10.1016\/S0960-9822(03)00358-0"},{"key":"97","doi-asserted-by":"crossref","unstructured":"97. Salinas              RK,                Bruschweiler-Li              L, Johnson              E,                Br\u00fcschweiler              R. 2011.            Ca2+ binding alters the interdomain flexibility between the two            cytoplasmic calcium-binding domains in the Na+\/Ca2+ exchanger.              <i>J Biol Chem<\/i>          286: 32123\u201332131.","DOI":"10.1074\/jbc.M111.249268"},{"key":"98","doi-asserted-by":"crossref","unstructured":"98. Sanders              KM. 2001.            Invited review: mechanisms of calcium handling in smooth            muscles. <i>J Appl Physiol<\/i>          91: 1438\u20131449.","DOI":"10.1152\/jappl.2001.91.3.1438"},{"key":"99","doi-asserted-by":"crossref","unstructured":"99. Schr\u00f6der              UH, Breder              J, Sabelhaus              CF, Reymann              KG. 1999.            The novel Na+\/Ca2+ exchange inhibitor KB-R7943 protects CA1 neurons in            rat hippocampal slices against hypoxic\/hypoglycemic injury.              <i>Neuropharmacology<\/i>          38: 319\u2013321.","DOI":"10.1016\/S0028-3908(98)00198-1"},{"key":"100","doi-asserted-by":"crossref","unstructured":"100. Scognamiglio              A, Corvino              A, Caliendo              G, Fiorino              F, Perissutti              E, Santagada              V, Severino              B. 2025.            Druggability of Sodium Calcium Exchanger (NCX): Challenges and Recent            Development. <i>Int J Mol Sci<\/i>          26: 8888.","DOI":"10.3390\/ijms26188888"},{"key":"101","doi-asserted-by":"crossref","unstructured":"101. Sharma              V, O\u2019Halloran              DM. 2014.            Recent structural and functional insights into the family of sodium            calcium exchangers. <i>Genesis<\/i>          52: 93\u2013109.","DOI":"10.1002\/dvg.22735"},{"key":"102","doi-asserted-by":"crossref","unstructured":"102. Soda              T, Brunetti              V,                Berra-Romani              R, Moccia              F. 2023.            The emerging role of N-Methyl-D-Aspartate (NMDA) receptors in the            cardiovascular system: physiological implications, pathological consequences, and            therapeutic perspectives. <i>Int J Mol            Sci<\/i>          24: 3914.","DOI":"10.3390\/ijms24043914"},{"key":"103","doi-asserted-by":"crossref","unstructured":"103. Solovyova              N,                Verkhratsky              A. 2002.            Monitoring of free calcium in the neuronal endoplasmic reticulum: an            overview of modern approaches. <i>J Neurosci              Methods<\/i>          122: 1\u201312.","DOI":"10.1016\/S0165-0270(02)00300-X"},{"key":"104","doi-asserted-by":"crossref","unstructured":"104. Sp\u00e4t              A, Szanda              G, Csord\u00e1s              G, Hajn\u00f3czky              G. 2008.            High- and low-calcium-dependent mechanisms of mitochondrial calcium            signalling. <i>Cell Calcium<\/i>          44: 51\u201363.","DOI":"10.1016\/j.ceca.2007.11.015"},{"key":"105","doi-asserted-by":"crossref","unstructured":"105. Takahashi              K, Takahashi              T, Suzuki              T, Onishi              M, Tanaka              Y,                Hamano-Takahashi              A, Ota              T, Kameo              K, Matsuda              T, Baba              A. 2003.            Protective effects of SEA0400, a novel and selective inhibitor of the            Na+\/Ca2+ exchanger, on myocardial ischemia-reperfusion injuries.              <i>Eur J Pharmacol<\/i>          458: 155\u2013162.","DOI":"10.1016\/S0014-2999(02)02732-2"},{"key":"106","doi-asserted-by":"crossref","unstructured":"106. Tang              WJ, Gilman              AG. 1992.            Adenylyl cyclases. <i>Cell<\/i>          70: 869\u2013872.","DOI":"10.1016\/0092-8674(92)90236-6"},{"key":"107","doi-asserted-by":"crossref","unstructured":"107. Thrower              EC, Hagar              RE, Ehrlich              BE. 2001.            Regulation of Ins1,4,5P3 receptor isoforms by endogenous            modulators. <i>Trends Pharmacol Sci<\/i>          22: 580\u2013586.","DOI":"10.1016\/S0165-6147(00)01809-5"},{"key":"108","doi-asserted-by":"crossref","unstructured":"108. Van                Eylen              F, Lebeau              C,                Albuquerque-Silva              J, Herchuelz              A. 1998.            Contribution of Na\/Ca exchange to Ca2+ outflow and entry in the rat            pancreatic beta-cell: studies with antisense oligonucleotides.              <i>Diabetes<\/i>          47: 1873\u20131880.","DOI":"10.2337\/diabetes.47.12.1873"},{"key":"109","doi-asserted-by":"crossref","unstructured":"109. Villaseca              S, Romero              G, Ruiz              MJ, P\u00e9rez              C, Leal              JI, Tovar              LM, Torrej\u00f3n              M. 2022.            G\u03b1i protein subunit: a step toward understanding its non-canonical            mechanisms. <i>Front Cell Dev Biol<\/i>          10: 941870.","DOI":"10.3389\/fcell.2022.941870"},{"key":"110","doi-asserted-by":"crossref","unstructured":"110. Wang              M, Sun              Y, Li              L, Wu              P, Dkw              O, Shi              H. 2021.            Calcium channels: noteworthy regulators and therapeutic targets in            dermatological diseases. <i>Front            Pharmacol<\/i>          12: 702264.","DOI":"10.3389\/fphar.2021.702264"},{"key":"111","doi-asserted-by":"crossref","unstructured":"111. Watano              T, Kimura              J, Morita              T, Nakanishi              H. 1996.            A novel antagonist, No. 7943, of the Na+\/Ca2+ exchange current in            guinea-pig cardiac ventricular cells. <i>Br J              Pharmacol<\/i>          119: 555\u2013563.","DOI":"10.1111\/j.1476-5381.1996.tb15708.x"},{"key":"112","doi-asserted-by":"crossref","unstructured":"112. Xue              J, Zeng              W, Han              Y, John              S, Ottolia              M, Jiang              Y. 2023.            Structural mechanisms of the human cardiac sodium-calcium exchanger            NCX1. <i>Nat Commun<\/i>          14: 6181.","DOI":"10.1038\/s41467-023-41885-4"},{"key":"113","doi-asserted-by":"crossref","unstructured":"113. Yamaguchi              Y, Katoh              H, Yasui              H, Aoki              J, Nakamura              K, Negishi              M. 2000.            Galpha(12) and galpha(13) inhibit Ca(2+)-dependent exocytosis through            Rho\/Rho-associated kinase-dependent pathway. <i>J              Neurochem<\/i>          75: 708\u2013717.","DOI":"10.1046\/j.1471-4159.2000.0750708.x"},{"key":"114","doi-asserted-by":"crossref","unstructured":"114. Yao              A, Su              Z, Nonaka              A, Zubair              I, Lu              L, Philipson              KD, Bridge              JHB, Barry              WH. 1998.            Effects of overexpression of the Na+-Ca2+ exchanger on [Ca2+]i transients            in murine ventricular myocytes. <i>Circ            Res<\/i>          82: 657\u2013665.","DOI":"10.1161\/01.RES.82.6.657"},{"key":"115","doi-asserted-by":"crossref","unstructured":"115. Zamponi              GW, Lewis              RJ, Todorovic              SM, Arneric              SP, Snutch              TP. 2009.            Role of voltage-gated calcium channels in ascending pain            pathways. <i>Brain Res Brain Res Rev<\/i>          60: 84\u201389.","DOI":"10.1016\/j.brainresrev.2008.12.021"}],"container-title":["Journal of Veterinary Medical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jvms\/88\/9\/88_26-0186\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:46:54Z","timestamp":1788583614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jvms\/88\/9\/88_26-0186\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":115,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1292\/jvms.26-0186","relation":{},"ISSN":["0916-7250","1347-7439"],"issn-type":[{"value":"0916-7250","type":"print"},{"value":"1347-7439","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"26-0186"}}