{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T12:11:32Z","timestamp":1793016692968,"version":"4.5.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2011,8,19]]},"abstract":"\n \n Rationale:<\/jats:underline>\n <\/jats:title>\n Neuronal calcium sensor-1 (NCS-1) regulates various neuronal functions. Although it is expressed in the heart, very little is known about its cardiac functions.<\/jats:p>\n <\/jats:sec>\n \n \n Objective:<\/jats:underline>\n <\/jats:title>\n This study aimed to identify the physiological and pathological roles of NCS-1 in the heart.<\/jats:p>\n <\/jats:sec>\n \n \n Methods and Results:<\/jats:underline>\n <\/jats:title>\n \n We characterized the cardiac functions of knockout mice (\n Ncs1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n ) and identified NCS-1 as a novel regulator of cardiac Ca\n 2+<\/jats:sup>\n signaling, specifically in immature and hypertrophic hearts. NCS-1 was highly expressed in young hearts, and its deletion decreased survival and contractile function in young mice. Intracellular Ca\n 2+<\/jats:sup>\n levels and sarcoplasmic reticulum Ca\n 2+<\/jats:sup>\n content were significantly lower in\n Ncs1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n myocytes than in wild-type cells. This was due to reduced Ca\n 2+<\/jats:sup>\n \/calmodulin-dependent protein kinase II (CaMKII) activity in\n Ncs1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n myocytes, which led to reduced sarcoplasmic reticulum Ca\n 2+<\/jats:sup>\n uptake and release. NCS-1 physically and functionally interacted with inositol 1,4,5-trisphosphate receptors (IP\n 3<\/jats:sub>\n Rs) in the heart. In addition, IP\n 3<\/jats:sub>\n R stimulation resulted in phosphorylation of CaMKII-\u03b4, which was enhanced by NCS-1 overexpression. These results suggest that a functional link exists between NCS-1, IP\n 3<\/jats:sub>\n R function, and CaMKII activation that may affect global Ca\n 2+<\/jats:sup>\n signals in the immature heart. Furthermore, NCS-1 was upregulated in hypertrophic hearts, and hormone-induced hypertrophy was largely prevented in\n Ncs1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n hearts. Inhibitors of IP\n 3<\/jats:sub>\n Rs, CaMKII, and calcineurin all prevented NCS-1\u2013induced hypertrophy, which suggests the involvement of these pathways.\n <\/jats:p>\n <\/jats:sec>\n \n \n Conclusions:<\/jats:underline>\n <\/jats:title>\n \n NCS-1 is an important regulator of immature heart function and hypertrophy, and it functions in part by promoting IP\n 3<\/jats:sub>\n R function, followed by CaMKII-dependent signal activation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circresaha.111.248864","type":"journal-article","created":{"date-parts":[[2011,7,8]],"date-time":"2011-07-08T11:17:00Z","timestamp":1310123820000},"page":"512-523","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Neuronal Calcium Sensor-1 Promotes Immature Heart Function and Hypertrophy by Enhancing Ca\n 2+<\/sup>\n Signals"],"prefix":"10.1161","volume":"109","author":[{"given":"Tomoe Y.","family":"Nakamura","sequence":"first","affiliation":[{"name":"From the Department of Molecular Physiology (T.Y.N., S.W.), National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; Banyan Biomarkers, Inc (A.J.), Alachua, FL; and Laboratory for Developmental Neurobiology (K.M.), RIKEN Brain Science Institute, Saitama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Jeromin","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Physiology (T.Y.N., S.W.), National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; Banyan Biomarkers, Inc (A.J.), Alachua, FL; and Laboratory for Developmental Neurobiology (K.M.), RIKEN Brain Science Institute, Saitama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Mikoshiba","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Physiology (T.Y.N., S.W.), National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; Banyan Biomarkers, Inc (A.J.), Alachua, FL; and Laboratory for Developmental Neurobiology (K.M.), RIKEN Brain Science Institute, Saitama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Physiology (T.Y.N., S.W.), National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; Banyan Biomarkers, Inc (A.J.), Alachua, FL; and Laboratory for Developmental Neurobiology (K.M.), RIKEN Brain Science Institute, Saitama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/415198a"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1990.259.2.H309"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.5.415"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(95)00158-1"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.74.2.354"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.05.014"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200809960"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.02.005"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3530001"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201132200"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221168498"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068278"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00434-2"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008603200"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-19-08476.2002"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000057203.72435.C9"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90267-U"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1117"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.08.014"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00276-8"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200508156"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.08.018"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.175141"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22466"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012500"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.220038"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27374"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001825107"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104048200"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.102889"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605536200"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.166033"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2181"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905485106"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.111.248864","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:34:55Z","timestamp":1715556895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.111.248864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,19]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,8,19]]}},"alternative-id":["10.1161\/CIRCRESAHA.111.248864"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.111.248864","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.11930958.13048056","asserted-by":"object"}]},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8,19]]},"assertion":[{"value":"2011-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-06-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-07-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}