{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:19:38Z","timestamp":1790651978477,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T00:00:00Z","timestamp":1562112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32\u2010GM008181"],"award-info":[{"award-number":["T32\u2010GM008181"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL102758"],"award-info":[{"award-number":["R01\u2010HL102758"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Circadian oscillations in spontaneous action potential firing in the suprachiasmatic nucleus (SCN) translate time\u2010of\u2010day throughout the mammalian brain.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The ion channels that regulate the circadian pattern of SCN firing have not been comprehensively identified.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Ca<jats:sup>2+<\/jats:sup> channels regulate action potential activity across many types of excitable cells, and the activity of L\u2010, N\u2010, P\/Q\u2010 and R\u2010type channels are required for normal daytime firing frequency in SCN neurons and circuit rhythms.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Only the L\u2010type Ca<jats:sup>2+<\/jats:sup> current exhibits a day <jats:italic>versus<\/jats:italic> night difference in current magnitude, providing insight into the mechanism that produces rhythmic action potential firing in SCN.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The mammalian circadian clock encodes time via rhythmic action potential activity in the suprachiasmatic nucleus (SCN) of the hypothalamus, which governs daily rhythms in physiology and behaviour. SCN neurons exhibit 24\u00a0h oscillations in spontaneous firing, with higher firing during day compared to night. Several ionic currents have been identified that regulate SCN firing, including voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> currents, but the circadian regulation of distinct voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> channel (VGCC) components has not been comprehensively addressed. In this study, whole\u2010cell L\u2010 (nimodipine\u2010sensitive), N\u2010 and P\/Q\u2010 (\u03c9\u2010agatoxin IVA, \u03c9\u2010conotoxin GVIA, \u03c9\u2010conotoxin MVIIC\u2010sensitive), R\u2010 (Ni<jats:sup>2+<\/jats:sup>\u2010sensitive) and T\u2010type (TTA\u2010P2\u2010sensitive) currents were recorded from day and night SCN slices. Using standard voltage protocols, Ni<jats:sup>2+<\/jats:sup>\u2010sensitive currents comprised the largest proportion of total VGCC current, followed by nimodipine\u2010, \u03c9\u2010agatoxin IVA\u2010, \u03c9\u2010conotoxin GVIA\u2010 and TTA\u2010P2\u2010sensitive currents. Only the nimodipine\u2010sensitive current exhibited a diurnal difference in magnitude, with daytime current larger than night. No diurnal variation was observed for the other Ca<jats:sup>2+<\/jats:sup> current subtypes. The difference in nimodipine\u2010sensitive current was due to larger peak current activated during the day, not differences in inactivation, and was eliminated by Bay K8644. Blocking L\u2010type channels decreased firing selectively during the day, consistent with higher current magnitudes, and reduced SCN circuit rhythmicity recorded by multi\u2010electrode arrays. Yet blocking N\u2010, P\/Q\u2010 and R\u2010type channels also decreased daytime firing, with little effect at night, and decreased circuit rhythmicity. These data identify a unique diurnal regulation of L\u2010type current among the major VGCC subtypes in SCN neurons, but also reveal that diurnal modulation is not required for time\u2010of\u2010day\u2010specific effects on firing and circuit rhythmicity.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp278327","type":"journal-article","created":{"date-parts":[[2019,6,9]],"date-time":"2019-06-09T06:43:50Z","timestamp":1560062630000},"page":"1775-1790","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Diurnal properties of voltage\u2010gated Ca<sup>2+<\/sup> currents in suprachiasmatic nucleus and roles in action potential firing"],"prefix":"10.1113","volume":"598","author":[{"given":"Beth A.","family":"McNally","sequence":"first","affiliation":[{"name":"Department of Physiology University of Maryland School of Medicine  Baltimore MD 21201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber 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