{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:58Z","timestamp":1780454278705,"version":"3.54.1"},"reference-count":79,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,1,14]],"date-time":"2015-01-14T00:00:00Z","timestamp":1421193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,2,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>The mammalian pineal gland is a neuroendocrine organ that responds to circadian and seasonal rhythms. Its major function is to secrete melatonin as a hormonal night signal in response to nocturnal delivery of noradrenaline from sympathetic neurons.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Culturing rat pinealocytes in noradrenaline for 24\u00a0h induced a low\u2010voltage activated transient Ca<jats:sup>2+<\/jats:sup>current whose pharmacology and kinetics corresponded to a Ca<jats:sub>V<\/jats:sub>3.1 T\u2010type channel.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The upregulation of the T\u2010type Ca<jats:sup>2+<\/jats:sup>current is initiated by \u03b2\u2010adrenergic receptors, cyclic AMP and cyclic AMP\u2010dependent protein kinase.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Messenger RNA for Ca<jats:sub>V<\/jats:sub>3.1 T\u2010type channels is significantly elevated by noradrenaline at 8\u00a0h and 24\u00a0h.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The noradrenaline\u2010induced T\u2010type channel mediated an increased Ca<jats:sup>2+<\/jats:sup>entry and supported modest transient electrical responses to depolarizing stimuli, revealing the potential for circadian regulation of pinealocyte electrical excitability and Ca<jats:sup>2+<\/jats:sup>signalling.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Our basic hypothesis is that mammalian pinealocytes have cycling electrical excitability and Ca<jats:sup>2+<\/jats:sup>signalling that may contribute to the circadian rhythm of pineal melatonin secretion. This study asked whether the functional expression of voltage\u2010gated Ca<jats:sup>2+<\/jats:sup>channels (Ca<jats:sub>V<\/jats:sub>channels) in rat pinealocytes is changed by culturing them in noradrenaline (NA) as a surrogate for the night signal. Channel activity was assayed as ionic currents under patch clamp and as optical signals from a Ca<jats:sup>2+<\/jats:sup>\u2010sensitive dye. Channel mRNAs were assayed by quantitative polymerase chain reaction. Cultured without NA, pinealocytes showed only non\u2010inactivating L\u2010type dihydropyridine\u2010sensitive Ca<jats:sup>2+<\/jats:sup>current. After 24\u00a0h in NA, additional low\u2010voltage activated transient Ca<jats:sup>2+<\/jats:sup>current developed whose pharmacology and kinetics corresponded to a T\u2010type Ca<jats:sub>V<\/jats:sub>3.1 channel. This change was initiated by \u03b2\u2010adrenergic receptors, cyclic AMP and protein kinase A as revealed by pharmacological experiments. mRNA for Ca<jats:sub>V<\/jats:sub>3.1 T\u2010type channels became significantly elevated, but mRNA for another T\u2010type channel and for the major L\u2010type channel did not change. After only 8\u00a0h of NA treatment, the Ca<jats:sub>V<\/jats:sub>3.1\u00a0mRNA was already elevated, but the transient Ca<jats:sup>2+<\/jats:sup>current was not. Even a 16\u00a0h wait without NA following the 8\u00a0h NA treatment induced little additional transient current. However, these cells were somehow primed to make transient current as a second NA exposure for only 60\u00a0min sufficed to induce large T\u2010type currents. The NA\u2010induced T\u2010type channel mediated an increased Ca<jats:sup>2+<\/jats:sup>entry during short depolarizations and supported modest transient electrical responses to depolarizing stimuli. Such experiments reveal the potential for circadian regulation of excitability.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.284208","type":"journal-article","created":{"date-parts":[[2014,12,13]],"date-time":"2014-12-13T03:13:37Z","timestamp":1418440417000},"page":"887-904","source":"Crossref","is-referenced-by-count":21,"title":["Noradrenaline upregulates T\u2010type calcium channels in rat pinealocytes"],"prefix":"10.1113","volume":"593","author":[{"given":"Haijie","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Bae","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Ryoung","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duk\u2010Su","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington Seattle WA USA"},{"name":"Department of Physics POSTECH Pohang Kyungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertil","family":"Hille","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1270"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017339"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2014.03.005"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808394200"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0937"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1989.tb24113.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(05)80006-5"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.27083"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1429"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.53.2.290"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-128-1-559"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702746200"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-04-03104.1995"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.138.5.2033"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0720073.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.140.12.5682"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0864"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2000.280401.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.51.4.551"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.1.103"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201210886"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66020748.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.1988.8.705"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2007.10.011"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414587200"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-002-0579-y"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.07.036"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.5.737"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508130200"},{"key":"e_1_2_6_32_1","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1523\/JNEUROSCI.09-07-02462.1989","article-title":"Voltage\u2010dependent calcium channels regulate melatonin output from cultured chick pineal cells","volume":"9","author":"Harrison NL","year":"1989","journal-title":"J Neurosci"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06457.x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1921"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.10.004"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00926.2006"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.00884.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.101402"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1420"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.05.013"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0894-08.2008"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.2.599"},{"key":"e_1_2_6_43_1","first-page":"307","article-title":"The melatonin rhythm\u2010generating enzyme: molecular regulation of serotonin N\u2010acetyltransferase in the pineal gland","volume":"52","author":"Klein DC","year":"1997","journal-title":"Recent Prog Horm Res"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00555.x"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-06-01912.1999"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(99)77134-1"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021930"},{"key":"e_1_2_6_48_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0022-3565(25)38950-0","article-title":"Beta\u20101 receptor is the predominant beta\u2010adrenoreceptor on rat brown adipose tissue","volume":"236","author":"Levin BE","year":"1986","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1740-3391-4-12"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi010763e"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2004.08.001"},{"key":"e_1_2_6_52_1","doi-asserted-by":"crossref","first-page":"12960","DOI":"10.1016\/S0021-9258(19)38253-5","article-title":"Molecular cloning and expression of the rat \u03b21\u2010adrenergic receptor gene","volume":"265","author":"Machida CA","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601261103"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0813"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.117440"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/36110"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02442.x"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0882"},{"key":"e_1_2_6_59_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0026-895X(25)08563-3","article-title":"Norepinephrine stimulation of pineal cyclic AMP response element\u2010binding protein phosphorylation: primary role of a \u03b2\u2010adrenergic receptor\/cyclic AMP mechanism","volume":"47","author":"Roseboom PH","year":"1995","journal-title":"Mol Pharmacol"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90664-1"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2005"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.2.2"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2007.10.007"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1159\/000327138"},{"key":"e_1_2_6_65_1","doi-asserted-by":"crossref","first-page":"11608","DOI":"10.1016\/S0021-9258(18)67286-2","article-title":"Essential role of calcium influx in the adrenergic regulation of cAMP and cGMP in rat pinealocytes","volume":"261","author":"Sugden AL","year":"1986","journal-title":"J Biol Chem"},{"key":"e_1_2_6_66_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0021-9258(19)75847-5","article-title":"\u03b11\u2010adrenoceptor activation elevates cytosolic calcium in rat pinealocytes by increasing net influx","volume":"262","author":"Sugden LA","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.062585499"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816X.2000.01324.x"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2781-11.2011"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.210248297"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(88)90194-4"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.6239"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1259-3"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(86)90042-4"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1996.tb00284.x"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2005-0888"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1999.82.5.2428"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00354.2013"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1180"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(94)90234-8"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2014.284208","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2014.284208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:32:31Z","timestamp":1747186351000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2014.284208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,14]]},"references-count":79,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,2,15]]}},"alternative-id":["10.1113\/jphysiol.2014.284208"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2014.284208","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,14]]}}}