{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:31:07Z","timestamp":1785803467298,"version":"3.56.0"},"reference-count":84,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Besides its role in the circadian rhythm, the pineal gland hormone melatonin (MLT) also possesses antiepileptogenic, antineoplastic, and cardioprotective properties, among others. The dosages necessary to elicit beneficial effects in these diseases often far surpass physiological concentrations. Although even high doses of MLT are considered to be largely harmless to humans, the possible side effects of pharmacological concentrations are so far not well investigated. In the present study, we report that pharmacological doses of MLT (3\u2009mM) strongly altered the electrophysiological characteristics of cultured primary mouse cerebellar granule cells (CGCs). Using whole\u2010cell patch clamp and ratiometric Ca<jats:sup>2+<\/jats:sup> imaging, we observed that pharmacological concentrations of MLT inhibited several types of voltage\u2010gated Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>, and Ca<jats:sup>2+<\/jats:sup> channels in CGCs independently of known MLT\u2010receptors, altering the character and pattern of elicited action potentials (APs) significantly, quickly and reversibly. Specifically, MLT reduced AP frequency, afterhyperpolarization, and rheobase, whereas AP amplitude and threshold potential remained unchanged. The altered biophysical profile of the cells could constitute a possible mechanism underlying the proposed beneficial effects of MLT in brain\u2010related disorders, such as epilepsy. On the other hand, it suggests potential adverse effects of pharmacological MLT concentrations on neurons, which should be considered when using MLT as a pharmacological compound.<\/jats:p>","DOI":"10.1111\/jpi.12919","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T19:36:12Z","timestamp":1696534572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Melatonin alters the excitability of mouse cerebellar granule neurons by inhibiting voltage\u2010gated sodium, potassium, and calcium channels"],"prefix":"10.1111","volume":"76","author":[{"given":"Karolos\u2010Philippos","family":"Pissas","sequence":"first","affiliation":[{"name":"Medical faculty Institute of Physiology, RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Schilling","sequence":"additional","affiliation":[{"name":"Medical faculty Institute of Physiology, RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Medical faculty Institute of Physiology, RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuemin","family":"Tian","sequence":"additional","affiliation":[{"name":"Medical faculty Institute of Physiology, RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7635-9883","authenticated-orcid":false,"given":"Stefan","family":"Gr\u00fcnder","sequence":"additional","affiliation":[{"name":"Medical faculty Institute of Physiology, RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12267"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2014.08.008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00083"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2007.00436.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2007.00518.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12548"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-019-03617-5"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.10.7074"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(99)00519-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/214919a0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27676"},{"key":"e_1_2_9_13_1","article-title":"Five year\u2010survival with high\u2010dose melatonin and other antitumor pineal hormones in advanced cancer patients eligible for the only palliative therapy","volume":"1","author":"Lissoni P","year":"2018","journal-title":"Research Journal of Oncology"},{"issue":"1","key":"e_1_2_9_14_1","article-title":"High dose melatonin therapy for patients with extremely intractable epilepsy","volume":"9","author":"Haginoya K","year":"2004","journal-title":"Neurol Asia"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12782"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12702"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13060943"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-016-0052-2"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700022009422"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002832"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)02188-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.02.023"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.03.068"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)76103-6"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12218"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010928117"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201902242R"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.03.012"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.33594\/000000022"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2015.01.009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(99)00110-0"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000257"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb09867.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.8.5245"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0035345"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.58.4.413"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00386161"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2019.07.016"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13950"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12294"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/8070"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02069.x"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-04-02995.1995"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1454-x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.009654"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2015.01.006"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2020.10.030"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb500086e"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2018.01.028"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.78.3.1631"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.80.2.493"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-28-09320.2003"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00478-9"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112611"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00611091"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.4.C923"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00467.x"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2018.10.014"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00002.2017"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-03-00949.1994"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1159\/000017370"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.251983"},{"issue":"9","key":"e_1_2_9_63_1","first-page":"2027","article-title":"Activation of conventional kinesin motors in clusters by Shaw voltage\u2010gated K+ channels","volume":"126","author":"Barry J","year":"2013","journal-title":"J Cell Sci"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-011-0279-9"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-8-65"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00437.2007"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0408-4"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.126367"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00206"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201711945"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7832825"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2013.09.013"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2011.01.018"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612054021006"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejbas.2015.05.003"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-010-9306-x"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12794"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4693-7"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2009.00727.x"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2010.00619.x"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030599"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14046597"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2019.1666455"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11030287"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00152"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12919","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T14:19:48Z","timestamp":1712585988000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,5]]},"references-count":84,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/jpi.12919"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12919","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,5]]},"assertion":[{"value":"2023-07-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12919"}}