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We examined the effects of citalopram on delayed rectifier outward K<jats:sup>+<\/jats:sup>current (I<jats:sub>K<\/jats:sub>) in mouse cortical neurons. Extracellular citalopram reversibly inhibited I<jats:sub>K<\/jats:sub>in a dose\u2010dependent manner and significantly shifted both steady\u2010state activation and inactivation curves toward hyperpolarization. Neither 5\u2010HT itself nor antagonists of 5\u2010HT and dopamine receptors could abolish citalopram\u2010induced inhibition of I<jats:sub>K<\/jats:sub>. In addition, intracellular application of GTP\u03b3\u2010S similarly failed to prevent the inhibition of I<jats:sub>K<\/jats:sub>by citalopram. When applied intracellularly, citalopram had no effect on I<jats:sub>K<\/jats:sub>and did not influence the reduction of I<jats:sub>K<\/jats:sub>induced by extracellular citalopram. The effect of citalopram was use dependent, but not frequency dependent, and it did not require channel opening. Electrophysiological recordings in acute cortical slice showed that citalopram significantly reduced the action potential (AP) firing frequency of cortical neurons and increased action potential duration (APD). The selective Kv2.1 subunit blocker Jingzhaotoxin\u2010III (JZTX\u2010III) did not abolish citalopram\u2010induced I<jats:sub>K<\/jats:sub>inhibition. Transfection of HEK293 cells with Kv2.1 or Kv2.2 constructs indicated that citalopram mainly inhibited Kv2.2 current. We suggest that citalopram\u2010induced inhibition of I<jats:sub>K<\/jats:sub>in mouse cortical neurons is independent of G\u2010protein\u2010coupled receptors and might exert its antidepressant effects by enhancing presynaptic efficiency. Our results may help to explain some of the unknown therapeutic effects of citalopram. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22744","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T23:14:55Z","timestamp":1317165295000},"page":"324-336","source":"Crossref","is-referenced-by-count":15,"title":["The antidepressant citalopram inhibits delayed rectifier outward K<sup>+<\/sup>current in mouse cortical neurons"],"prefix":"10.1002","volume":"90","author":[{"given":"Xiao\u2010Qin","family":"Zhan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Lin","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin\u2010Jing","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010Li","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Ai","family":"Mei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,9,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199603001-00002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-05-01473.2001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00088-0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.05.065"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013366"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-2-00019.xm"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300686"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.2041"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(04)65009-4"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-007-9230-5"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.128454"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.33549\/physiolres.930216","article-title":"Citalopram inhibits L\u2010type calcium channel current in rat cardiomyocytes in culture","volume":"51","author":"Hamplova\u2010Peichlova J","year":"2002","journal-title":"Physiol Res"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.159160"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199403001-00004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.153734"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v61n1202"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.074260"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.117747"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77727-6"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00373833"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.026419"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hup.470100903"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2007.03.006"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77624-6"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0022-3565(24)29415-5","article-title":"S33005, a novel ligand at both serotonin and norepinephrine transporters: I. 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