{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:04:53Z","timestamp":1791259493620,"version":"4.1.0"},"reference-count":46,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":2408,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.5\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:p>Calcium is important in controlling nuclear gene expression through the activation of multiple signal-transduction pathways in neurons. Compared with other voltage-gated calcium channels, CaV1 channels demonstrate a considerable advantage in signalling to the nucleus. In this review, we summarize the recent progress in elucidating the mechanisms involved. CaV1 channels, already advantaged in their responsiveness to depolarization, trigger communication with the nucleus by attracting colocalized clusters of activated CaMKII (Ca2+\/calmodulin-dependent protein kinase II). CaV2 channels lack this ability, but must work at a distance of &amp;gt;1\u00a0\u03bcm from the CaV1-CaMKII co-clusters, which hampers their relative efficiency for a given rise in bulk [Ca2+]i (intracellular [Ca2+]). Moreover, Ca2+ influx from CaV2 channels is preferentially buffered by the ER (endoplasmic reticulum) and mitochondria, further attenuating their effectiveness in signalling to the nucleus.<\/jats:p>","DOI":"10.1042\/bsr20120099","type":"journal-article","created":{"date-parts":[[2012,10,24]],"date-time":"2012-10-24T08:31:58Z","timestamp":1351067518000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Exploring the dominant role of Cav1 channels in signalling to the nucleus"],"prefix":"10.1042","volume":"33","author":[{"given":"Huan","family":"Ma","sequence":"first","affiliation":[{"name":"NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Cohen","sequence":"additional","affiliation":[{"name":"NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boxing","family":"Li","sequence":"additional","affiliation":[{"name":"NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard\u00a0W.","family":"Tsien","sequence":"additional","affiliation":[{"name":"NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,12,20]]},"reference":[{"key":"2021111619065708600_B1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0896-6273(02)00828-0","article-title":"Function and regulation of CREB family transcription factors in the nervous system","volume":"35","author":"Lonze","year":"2002","journal-title":"Neuron"},{"key":"2021111619065708600_B2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tins.2005.06.005","article-title":"The many faces of CREB","volume":"28","author":"Carlezon","year":"2005","journal-title":"Trends Neurosci."},{"key":"2021111619065708600_B3","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.1038\/sj.bjp.0706442","article-title":"A short history of voltage-gated calcium channels","volume":"147","author":"Dolphin","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"2021111619065708600_B4","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0165-6147(91)90595-J","article-title":"Molecular diversity of voltage-dependent Ca2+ channels","volume":"12","author":"Tsien","year":"1991","journal-title":"Trends Pharmacol. Sci."},{"key":"2021111619065708600_B5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1146\/annurev.cellbio.16.1.521","article-title":"Structure and regulation of voltage-gated Ca2+ channels","volume":"16","author":"Catterall","year":"2000","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2021111619065708600_B6","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0959-4388(03)00076-X","article-title":"Signaling from synapse to nucleus: the logic behind the mechanisms","volume":"13","author":"Deisseroth","year":"2003","journal-title":"Curr. Opin. Neurobiol."},{"key":"2021111619065708600_B7","doi-asserted-by":"crossref","first-page":"PE4","DOI":"10.1126\/stke.2003.166.pe4","article-title":"Excitation-transcription coupling: signaling by ion channels to the nucleus","volume":"2003","author":"Dolmetsch","year":"2003","journal-title":"Sci. STKE"},{"key":"2021111619065708600_B8","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/0896-6273(91)90375-A","article-title":"L-type voltage-sensitive calcium channels mediate synaptic activation of immediate early genes","volume":"7","author":"Murphy","year":"1991","journal-title":"Neuron"},{"key":"2021111619065708600_B9","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/nrn987","article-title":"Regulation of transcription factors by neuronal activity","volume":"3","author":"West","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"2021111619065708600_B10","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nrn1749","article-title":"Late-phase long-term potentiation: getting to the nucleus","volume":"6","author":"Adams","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"2021111619065708600_B11","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3181\/0709-MR-241","article-title":"Action potentials: to the nucleus and beyond","volume":"233","author":"Saha","year":"2008","journal-title":"Exp. Biol. Med."},{"key":"2021111619065708600_B12","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/88380","article-title":"A calcium microdomain near NMDA receptors: on switch for ERK-dependent synapse-to-nucleus communication","volume":"4","author":"Hardingham","year":"2001","journal-title":"Nat. Neurosci."},{"key":"2021111619065708600_B13","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/385260a0","article-title":"Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression","volume":"385","author":"Hardingham","year":"1997","journal-title":"Nature"},{"key":"2021111619065708600_B14","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tins.2005.06.005","article-title":"The many faces of CREB","volume":"28","author":"Carlezon","year":"2005","journal-title":"Trends Neurosci."},{"key":"2021111619065708600_B15","first-page":"639","article-title":"Action of gamma-aminobutyric acid (GABA) on rat sympathetic-ganlion cells","volume":"47","author":"Adams","year":"1973","journal-title":"Br. J. Pharmacol."},{"key":"2021111619065708600_B16","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1083\/jcb.200805048","article-title":"CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation-transcription coupling","volume":"183","author":"Wheeler","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021111619065708600_B17","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.cell.2012.03.041","article-title":"CaV1 and CaV2 channels engage distinct modes of Ca2+ signaling to control CREB-dependent gene expression","volume":"149","author":"Wheeler","year":"2012","journal-title":"Cell"},{"key":"2021111619065708600_B18","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1083\/jcb.59.2.329","article-title":"Primary cultures of disociated sympathetic neurons. 1. Establishement of long-term grouth in culture and studies of differentiated properties","volume":"59","author":"Mains","year":"1973","journal-title":"J. Cell Biol."},{"key":"2021111619065708600_B19","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/0166-2236(94)90157-0","article-title":"Modulation of ion-channel funtion by G-protein-coupled receptors","volume":"17","author":"Hille","year":"1994","journal-title":"Trends Neurosci."},{"key":"2021111619065708600_B20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1523\/JNEUROSCI.07-02-00311.1987","article-title":"Stimulation of adenylate cyclase in relation to dopamine-induced long-term enhancement (LTE) of muscarinic depolarization in the rabbit superior cervical ganglion","volume":"7","author":"Mochida","year":"1987","journal-title":"J. Neurosci."},{"key":"2021111619065708600_B21","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.neures.2006.12.015","article-title":"A cholinergic model synapse to elucidate protein function at presynaptic terminals","volume":"57","author":"Ma","year":"2007","journal-title":"Neurosci. Res."},{"key":"2021111619065708600_B22","doi-asserted-by":"crossref","first-page":"13019","DOI":"10.1523\/JNEUROSCI.2517-09.2009","article-title":"KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons","volume":"29","author":"Ma","year":"2009","journal-title":"J. Neurosci."},{"key":"2021111619065708600_B23","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1074\/jbc.M803691200","article-title":"Dynamin and activity regulate synaptic vesicle recycling in sympathetic neurons","volume":"284","author":"Lu","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021111619065708600_B24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.neures.2011.02.004","article-title":"Excitation-transcription coupling in sympathetic neurons and the molecular mechanism of its initiation","volume":"70","author":"Ma","year":"2011","journal-title":"Neurosci. Res."},{"key":"2021111619065708600_B25","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1126\/science.3749894","article-title":"Stimulation of neuronal acetylcholine receptors induces rapid gene transcription","volume":"234","author":"Greenberg","year":"1986","journal-title":"Science"},{"key":"2021111619065708600_B26","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/322552a0","article-title":"Role of ion flux in the control of c-fos expression","volume":"322","author":"Morgan","year":"1986","journal-title":"Nature"},{"key":"2021111619065708600_B27","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1113\/jphysiol.1992.sp019035","article-title":"Dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels in a mammalian neuroblastoma-glioma cell line","volume":"448","author":"Kasai","year":"1992","journal-title":"J. Physiol."},{"key":"2021111619065708600_B28","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1113\/jphysiol.2003.051110","article-title":"Decoding of synaptic voltage waveforms by specific classes of recombinant high-threshold Ca2+ channels","volume":"553","author":"Liu","year":"2003","journal-title":"J. Physiol."},{"key":"2021111619065708600_B29","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0896-6273(00)80026-4","article-title":"Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity","volume":"16","author":"Deisseroth","year":"1996","journal-title":"Neuron"},{"key":"2021111619065708600_B30","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/363074a0","article-title":"Spatial calcium buffering in saccular hair cells","volume":"363","author":"Roberts","year":"1993","journal-title":"Nature"},{"key":"2021111619065708600_B31","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0143-4160(92)90046-U","article-title":"Buffering of calcium in the vicinity of a channel pore","volume":"13","author":"Stern","year":"1992","journal-title":"Cell Calcium"},{"key":"2021111619065708600_B32","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1021\/bi00552a018","article-title":"New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures","volume":"19","author":"Tsien","year":"1980","journal-title":"Biochemistry"},{"key":"2021111619065708600_B33","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/978-3-642-70744-5_8","article-title":"Concentration profiles of intracellular calcium in the presence of a diffusible chelator","volume-title":"Calcium Electrogenesis and Neuronal Functioning (Experimental Brain Research Series)","author":"Neher","year":"1986"},{"key":"2021111619065708600_B34","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/S0959-4388(98)80067-6","article-title":"Mitochondrial oversight of cellular Ca2+ signaling","volume":"8","author":"Babcock","year":"1998","journal-title":"Curr. Opin. Neurobiol."},{"key":"2021111619065708600_B35","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1523\/JNEUROSCI.14-07-04007.1994","article-title":"An FCCP-sensitive Ca2+ store in bullfrog sympathetic neurons and its participation in stimulus-evoked changes in [Ca2+]i","volume":"14","author":"Friel","year":"1994","journal-title":"J. Neurosci."},{"key":"2021111619065708600_B36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1113\/jphysiol.1990.sp018094","article-title":"Regulation of the intracellular free calcium concentration in single rat dorsal root ganglion neurones in\u00a0vitro","volume":"425","author":"Thayer","year":"1990","journal-title":"J. Physiol."},{"key":"2021111619065708600_B37","doi-asserted-by":"crossref","first-page":"177","DOI":"10.4067\/S0716-97602002000200008","article-title":"Calcium signal compartmentalization","volume":"35","author":"Petersen","year":"2002","journal-title":"Biol. Res."},{"key":"2021111619065708600_B38","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/S0959-4388(98)80067-6","article-title":"Mitochondrial oversight of cellular Ca2+ signaling","volume":"8","author":"Babcock","year":"1998","journal-title":"Curr. Opin. Neurobiol."},{"key":"2021111619065708600_B39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ceca.2005.06.011","article-title":"Mitochondria and calcium signaling","volume":"38","author":"Nicholls","year":"2005","journal-title":"Cell Calcium"},{"key":"2021111619065708600_B40","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nature02246","article-title":"The mitochondrial calcium uniporter is a highly selective ion channel","volume":"427","author":"Kirichok","year":"2004","journal-title":"Nature"},{"key":"2021111619065708600_B41","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/35000001","article-title":"Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion","volume":"2","author":"Montero","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"2021111619065708600_B42","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1054\/ceca.1999.0076","article-title":"Mitochondria as biosensors of calcium microdomains","volume":"26","author":"Rizzuto","year":"1999","journal-title":"Cell Calcium"},{"key":"2021111619065708600_B43","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1126\/science.8235595","article-title":"Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria","volume":"262","author":"Rizzuto","year":"1993","journal-title":"Science"},{"key":"2021111619065708600_B44","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1126\/science.1063395","article-title":"Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway","volume":"294","author":"Dolmetsch","year":"2001","journal-title":"Science"},{"key":"2021111619065708600_B45","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1523\/JNEUROSCI.23-08-03446.2003","article-title":"Interactions with PDZ proteins are required for L-type calcium channels to activate cAMP response element-binding protein-dependent gene expression","volume":"23","author":"Weick","year":"2003","journal-title":"J. Neurosci."},{"key":"2021111619065708600_B46","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.neuron.2007.06.032","article-title":"AKAP79\/150 anchoring of calcineurin controls neuronal L-type Ca2+ channel activity and nuclear signaling","volume":"55","author":"Oliveria","year":"2007","journal-title":"Neuron"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20120099\/475578\/bsr033e009.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20120099\/475578\/bsr033e009.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T19:51:44Z","timestamp":1637092304000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/33\/1\/e00009\/82069\/Exploring-the-dominant-role-of-Cav1-channels-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,20]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,2,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20120099","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,20]]},"article-number":"e00009"}}