title: Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-CaV 1.3-RyR pathway in the mouse.
abstract: Histamine, a neurotransmitter/neuromodulator implicated in the control of arousal state, exerts a potent phase-shifting effect on the circadian clock in the rodent suprachiasmatic nucleus (SCN). In this study, the mechanisms by which histamine resets the circadian clock in the mouse SCN were investigated. As a first step, Ca(2+) -imaging techniques were used to demonstrate that histamine increases intracellular Ca(2+) concentration ([Ca(2+) ]i ) in acutely dissociated SCN neurons and that this increase is blocked by the H1 histamine receptor (H1R) antagonist pyrilamine, the removal of extracellular Ca(2+) and the L-type Ca(2+) channel blocker nimodipine. The histamine-induced Ca(2+) transient is reduced, but not blocked, by application of the ryanodine receptor (RyR) blocker dantrolene. Immunohistochemical techniques indicated that CaV 1.3 L-type Ca(2+) channels are expressed mainly in the somata of SCN cells along with the H1R, whereas CaV 1.2 channels are located primarily in the processes. Finally, extracellular single-unit recordings demonstrated that the histamine-elicited phase delay of the circadian neural activity rhythm recorded from SCN slices is blocked by pyrilamine, nimodipine and the knockout of CaV 1.3 channel. Again, application of dantrolene reduced but did not block the histamine-induced phase delays. Collectively, these results indicate that, to reset the circadian clock, histamine increases [Ca(2+) ]i in SCN neurons by activating CaV 1.3 channels through H1R, and secondarily by causing Ca(2+) -induced Ca(2+) release from RyR-mediated internal stores.
authors.affiliation: Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Korea.
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Korea.
authors.forename: Young-Beom
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Korea.
authors.forename: Woong Bin
authors.initials: WB
authors.lastname: Kim
authors.affiliation: Center for Neural Science and Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, 136-791, Korea.|Department of Nanobiomedical Science, Dankook University, Chungnam, Korea.
authors.forename: Bo-Eun
authors.initials: BE
authors.lastname: Yoon
authors.affiliation: Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Korea.
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Shen
authors.affiliation: Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Korea.
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore Bik MD9, Singapore, Singapore.
authors.forename: Tuck-Wah
authors.initials: TW
authors.lastname: Soong
authors.affiliation: Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Korea.
authors.forename: Hee-Chul
authors.initials: HC
authors.lastname: Han
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California-Los Angeles, Los Angeles, CA, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Colwell
authors.affiliation: Center for Neural Science and Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, 136-791, Korea.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Korea.
authors.forename: Yang In
authors.initials: YI
authors.lastname: Kim
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D057906:Circadian Clocks / Q000502:physiology*; D003620:Dantrolene / Q000494:pharmacology; D006632:Histamine / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009553:Nimodipine / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*
chemical_list: C485995:Cacna1d protein, mouse; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D019837:Ryanodine Receptor Calcium Release Channel; D009553:Nimodipine; D006632:Histamine; D003620:Dantrolene; D011738:Pyrilamine
keywords: brain slice; calcium; dantrolene; electrophysiology; nimodipine