{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:42:03Z","timestamp":1792680123121,"version":"4.5.0"},"reference-count":110,"publisher":"Society for Neuroscience","issue":"17","license":[{"start":{"date-parts":[[2013,10,24]],"date-time":"2013-10-24T00:00:00Z","timestamp":1382572800000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2013,4,24]]},"abstract":"<jats:p>Intracellular Ca<jats:sup>2+<\/jats:sup>is a key regulator of life or death decisions in cultured neurons and sensory cells. The role of Ca<jats:sup>2+<\/jats:sup>in these processes is less clear<jats:italic>in vivo<\/jats:italic>, as the location of these cells often impedes visualization of intracellular Ca<jats:sup>2+<\/jats:sup>dynamics. We generated transgenic zebrafish lines that express the genetically encoded Ca<jats:sup>2+<\/jats:sup>indicator GCaMP in mechanosensory hair cells of the lateral line. These lines allow us to monitor intracellular Ca<jats:sup>2+<\/jats:sup>dynamics in real time during aminoglycoside-induced hair cell death. After exposure of live larvae to aminoglycosides, dying hair cells undergo a transient increase in intracellular Ca<jats:sup>2+<\/jats:sup>that occurs shortly after mitochondrial membrane potential collapse. Inhibition of intracellular Ca<jats:sup>2+<\/jats:sup>elevation through either caged chelators or pharmacological inhibitors of Ca<jats:sup>2+<\/jats:sup>effectors mitigates toxic effects of aminoglycoside exposure. Conversely, artificial elevation of intracellular Ca<jats:sup>2+<\/jats:sup>by caged Ca<jats:sup>2+<\/jats:sup>release agents sensitizes hair cells to the toxic effects of aminoglycosides. These data suggest that alterations in intracellular Ca<jats:sup>2+<\/jats:sup>homeostasis play an essential role in aminoglycoside-induced hair cell death, and indicate several potential therapeutic targets to stem ototoxicity.<\/jats:p>","DOI":"10.1523\/jneurosci.4559-12.2013","type":"journal-article","created":{"date-parts":[[2013,4,24]],"date-time":"2013-04-24T17:23:53Z","timestamp":1366824233000},"page":"7513-7525","source":"Crossref","is-referenced-by-count":90,"title":["Disruption of Intracellular Calcium Regulation Is Integral to Aminoglycoside-Induced Hair Cell Death"],"prefix":"10.1523","volume":"33","author":[{"given":"Robert","family":"Esterberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale W.","family":"Hailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison B.","family":"Coffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Raible","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin W.","family":"Rubel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2013,4,24]]},"reference":[{"key":"2023041304035248000_33.17.7513.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2601-12.2012"},{"key":"2023041304035248000_33.17.7513.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022347"},{"key":"2023041304035248000_33.17.7513.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2011.00728.x"},{"key":"2023041304035248000_33.17.7513.4","doi-asserted-by":"publisher","DOI":"10.1086\/520961"},{"key":"2023041304035248000_33.17.7513.5","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32834ed882"},{"key":"2023041304035248000_33.17.7513.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.8097060"},{"key":"2023041304035248000_33.17.7513.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(96)00167-0"},{"key":"2023041304035248000_33.17.7513.8","doi-asserted-by":"publisher","DOI":"10.1007\/BF00603825"},{"key":"2023041304035248000_33.17.7513.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2004.11.003"},{"key":"2023041304035248000_33.17.7513.10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.170092"},{"key":"2023041304035248000_33.17.7513.11","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-011-4200-z"},{"key":"2023041304035248000_33.17.7513.12","first-page":"601","article-title":"Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide","volume":"15","author":"Cianfrone","year":"2011","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2023041304035248000_33.17.7513.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"2023041304035248000_33.17.7513.14","doi-asserted-by":"publisher","DOI":"10.1089\/zeb.2009.0639"},{"key":"2023041304035248000_33.17.7513.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(97)00171-8"},{"key":"2023041304035248000_33.17.7513.16","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10258"},{"key":"2023041304035248000_33.17.7513.17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.11.6092"},{"key":"2023041304035248000_33.17.7513.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.05.007"},{"key":"2023041304035248000_33.17.7513.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(02)00338-6"},{"key":"2023041304035248000_33.17.7513.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(01)00417-8"},{"key":"2023041304035248000_33.17.7513.21","doi-asserted-by":"crossref","first-page":"5066","DOI":"10.1523\/JNEUROSCI.21-14-05066.2001","article-title":"Plasma membrane Ca2+-ATPase isoform 2a is the PMCA of hair bundles","volume":"21","author":"Dumont","year":"2001","journal-title":"J Neurosci"},{"key":"2023041304035248000_33.17.7513.22","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-6417-3"},{"key":"2023041304035248000_33.17.7513.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2005.10.003"},{"key":"2023041304035248000_33.17.7513.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79644-3"},{"key":"2023041304035248000_33.17.7513.25","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(92)90103-F"},{"key":"2023041304035248000_33.17.7513.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.09.004"},{"key":"2023041304035248000_33.17.7513.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.02.006"},{"key":"2023041304035248000_33.17.7513.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.010"},{"key":"2023041304035248000_33.17.7513.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2012.02.008"},{"key":"2023041304035248000_33.17.7513.30","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2002"},{"key":"2023041304035248000_33.17.7513.31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1124-08.2008"},{"key":"2023041304035248000_33.17.7513.32","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1523\/JNEUROSCI.23-11-04577.2003","article-title":"The distribution of calcium buffering proteins in the turtle cochlea","volume":"23","author":"Hackney","year":"2003","journal-title":"J Neurosci"},{"key":"2023041304035248000_33.17.7513.33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1196-05.2005"},{"key":"2023041304035248000_33.17.7513.34","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005579"},{"key":"2023041304035248000_33.17.7513.35","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-002-3022-x"},{"key":"2023041304035248000_33.17.7513.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(83)02019-4"},{"key":"2023041304035248000_33.17.7513.37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08657.x"},{"key":"2023041304035248000_33.17.7513.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811258106"},{"key":"2023041304035248000_33.17.7513.39","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00019.2007"},{"key":"2023041304035248000_33.17.7513.40","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1093\/oxfordjournals.jbchem.a135004","article-title":"Direct interaction of calmodulin antagonists with Ca2+\/calmodulin-dependent cyclic nucleotide phosphodiesterase","volume":"96","author":"Itoh","year":"1984","journal-title":"J Biochem"},{"key":"2023041304035248000_33.17.7513.41","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2597"},{"key":"2023041304035248000_33.17.7513.42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038471"},{"key":"2023041304035248000_33.17.7513.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1983.tb07292.x"},{"key":"2023041304035248000_33.17.7513.44","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1995.tb09986.x"},{"key":"2023041304035248000_33.17.7513.45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.2.638"},{"key":"2023041304035248000_33.17.7513.46","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4914-07.2008"},{"key":"2023041304035248000_33.17.7513.47","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-010-9193-8"},{"key":"2023041304035248000_33.17.7513.48","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.123604"},{"key":"2023041304035248000_33.17.7513.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.10.017"},{"key":"2023041304035248000_33.17.7513.50","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90239-N"},{"key":"2023041304035248000_33.17.7513.51","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.2009.01123.x"},{"key":"2023041304035248000_33.17.7513.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.08.021"},{"key":"2023041304035248000_33.17.7513.53","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00486.2004"},{"key":"2023041304035248000_33.17.7513.54","doi-asserted-by":"publisher","DOI":"10.1002\/biof.150"},{"key":"2023041304035248000_33.17.7513.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2009.06.005"},{"key":"2023041304035248000_33.17.7513.56","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20054"},{"key":"2023041304035248000_33.17.7513.57","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200512141"},{"key":"2023041304035248000_33.17.7513.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2004.05.003"},{"key":"2023041304035248000_33.17.7513.59","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.79.1.137"},{"key":"2023041304035248000_33.17.7513.60","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00659-1"},{"key":"2023041304035248000_33.17.7513.61","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.209.89"},{"key":"2023041304035248000_33.17.7513.62","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physrev.2000.80.1.315","article-title":"Mitochondria and neuronal survival","volume":"80","author":"Nicholls","year":"2000","journal-title":"Physiol Rev"},{"key":"2023041304035248000_33.17.7513.63","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1042\/bss0660055","article-title":"Excitotoxicity and mitochondria","volume":"66","author":"Nicholls","year":"1999","journal-title":"Biochem Soc Symp"},{"key":"2023041304035248000_33.17.7513.64","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5230-07.2008"},{"key":"2023041304035248000_33.17.7513.65","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1150"},{"key":"2023041304035248000_33.17.7513.66","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1976.tb04478.x"},{"key":"2023041304035248000_33.17.7513.67","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310331200"},{"key":"2023041304035248000_33.17.7513.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2010.01.001"},{"key":"2023041304035248000_33.17.7513.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2012.01.009"},{"key":"2023041304035248000_33.17.7513.70","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80612-3"},{"key":"2023041304035248000_33.17.7513.71","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21345"},{"key":"2023041304035248000_33.17.7513.72","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(01)00356-2"},{"key":"2023041304035248000_33.17.7513.73","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308367200"},{"key":"2023041304035248000_33.17.7513.74","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705477200"},{"key":"2023041304035248000_33.17.7513.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2006.05.005"},{"key":"2023041304035248000_33.17.7513.76","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.308"},{"key":"2023041304035248000_33.17.7513.77","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.072249"},{"key":"2023041304035248000_33.17.7513.78","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/BF00216440","article-title":"Immunocytochemical detection of calcium-binding protein in the cochlear and vestibular hair cells of the rat","volume":"232","author":"Rabi\u00e9","year":"1983","journal-title":"Cell Tissue Res"},{"key":"2023041304035248000_33.17.7513.79","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(20000529)421:2<189::AID-CNE5>3.0.CO;2-K"},{"key":"2023041304035248000_33.17.7513.80","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323844"},{"key":"2023041304035248000_33.17.7513.81","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.058545"},{"key":"2023041304035248000_33.17.7513.82","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.021507.105852"},{"key":"2023041304035248000_33.17.7513.83","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1113\/jphysiol.1976.sp011366","article-title":"Measurement of potassium and chloride ion concentrations in the cupulae of the lateral lines of Xenopus laevis","volume":"257","author":"Russell","year":"1976","journal-title":"J Physiol"},{"key":"2023041304035248000_33.17.7513.84","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.71062349.x"},{"key":"2023041304035248000_33.17.7513.85","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-3279-4_9"},{"key":"2023041304035248000_33.17.7513.86","doi-asserted-by":"publisher","DOI":"10.1126\/science.386513"},{"key":"2023041304035248000_33.17.7513.87","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043899"},{"key":"2023041304035248000_33.17.7513.88","doi-asserted-by":"publisher","DOI":"10.1080\/00016480310001312"},{"key":"2023041304035248000_33.17.7513.89","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1523\/JNEUROSCI.18-04-01230.1998","article-title":"Calmodulin is involved in membrane depolarization-mediated survival of motoneurons by phosphatidylinositol-3 kinase- and MAPK-independent pathways","volume":"18","author":"Soler","year":"1998","journal-title":"J Neurosci"},{"key":"2023041304035248000_33.17.7513.90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000238"},{"key":"2023041304035248000_33.17.7513.91","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(96)00101-3"},{"key":"2023041304035248000_33.17.7513.92","doi-asserted-by":"publisher","DOI":"10.1038\/1284"},{"key":"2023041304035248000_33.17.7513.93","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.22.6349"},{"key":"2023041304035248000_33.17.7513.94","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2010.01.003"},{"key":"2023041304035248000_33.17.7513.95","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1398"},{"key":"2023041304035248000_33.17.7513.96","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.02.052"},{"key":"2023041304035248000_33.17.7513.97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/JNEUROSCI.21-01-00001.2001","article-title":"A calcium-dependent feedback mechanism participates in shaping single NMDA miniature EPSCs","volume":"21","author":"Umemiya","year":"2001","journal-title":"J Neurosci"},{"key":"2023041304035248000_33.17.7513.98","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112917"},{"key":"2023041304035248000_33.17.7513.99","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(84)90041-8"},{"key":"2023041304035248000_33.17.7513.100","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(84)90087-X"},{"key":"2023041304035248000_33.17.7513.101","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(90)90060-L"},{"key":"2023041304035248000_33.17.7513.102","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0b013e32833e05ec"},{"key":"2023041304035248000_33.17.7513.103","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.11.014"},{"key":"2023041304035248000_33.17.7513.104","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1302"},{"key":"2023041304035248000_33.17.7513.105","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)15012-0"},{"key":"2023041304035248000_33.17.7513.106","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200506189"},{"key":"2023041304035248000_33.17.7513.107","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1152\/jn.1996.76.6.4127","article-title":"Eighth nerve activity regulates intracellular calcium concentration of avian cochlear nucleus neurons via a metabotropic glutamate receptor","volume":"76","author":"Zirpel","year":"1996","journal-title":"J Neurophysiol"},{"key":"2023041304035248000_33.17.7513.108","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1523\/JNEUROSCI.15-01-00214.1995","article-title":"Activation of a metabotropic glutamate receptor increases intracellular calcium concentrations in neurons of the avian cochlear nucleus","volume":"15","author":"Zirpel","year":"1995","journal-title":"J Neurosci"},{"key":"2023041304035248000_33.17.7513.109","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1152\/jn.1998.79.5.2288","article-title":"Activity-dependent regulation of [Ca2+]i in avian cochlear nucleus neurons: roles of protein kinases A and C and relation to cell death","volume":"79","author":"Zirpel","year":"1998","journal-title":"J Neurophysiol"},{"key":"2023041304035248000_33.17.7513.110","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61109-7"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.4559-12.2013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T21:38:24Z","timestamp":1681421904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.4559-12.2013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,24]]},"references-count":110,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2013,4,24]]},"published-print":{"date-parts":[[2013,4,24]]}},"alternative-id":["10.1523\/JNEUROSCI.4559-12.2013"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.4559-12.2013","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,24]]}}}