Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-Ca<inf>V</inf>1.3-RyR pathway in the mouse

Yoon Sik Kim, Young Beom Kim, Woong Bin Kim, Bo Eun Yoon, Feng Yan Shen, Seung Won Lee, Tuck Wah Soong, Hee Chul Han, Christopher S. Colwell, Changjoon Lee, Yang In Kim

Research output: Contribution to journalArticle

9 Citations (Scopus)

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<sup>2+</sup>-imaging techniques were used to demonstrate that histamine increases intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<inf>i</inf>) in acutely dissociated SCN neurons and that this increase is blocked by the H1 histamine receptor (H1R) antagonist pyrilamine, the removal of extracellular Ca<sup>2+</sup> and the L-type Ca<sup>2+</sup> channel blocker nimodipine. The histamine-induced Ca<sup>2+</sup> transient is reduced, but not blocked, by application of the ryanodine receptor (RyR) blocker dantrolene. Immunohistochemical techniques indicated that Ca<inf>V</inf>1.3 L-type Ca<sup>2+</sup> channels are expressed mainly in the somata of SCN cells along with the H1R, whereas Ca<inf>V</inf>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 Ca<inf>V</inf>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<sup>2+</sup>]<inf>i</inf> in SCN neurons by activating Ca<inf>V</inf>1.3 channels through H1R, and secondarily by causing Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release from RyR-mediated internal stores.

Original languageEnglish
JournalEuropean Journal of Neuroscience
DOIs
Publication statusAccepted/In press - 2015

Fingerprint

Histamine H1 Receptors
Ryanodine Receptor Calcium Release Channel
Circadian Clocks
Suprachiasmatic Nucleus
Histamine
Dantrolene
Pyrilamine
Nimodipine
Neurotransmitter Agents
Histamine H1 Antagonists
Neurons
Carisoprodol
Arousal
Rodentia

Keywords

  • Brain slice
  • Calcium
  • Dantrolene
  • Electrophysiology
  • Nimodipine

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-Ca<inf>V</inf>1.3-RyR pathway in the mouse. / Kim, Yoon Sik; Kim, Young Beom; Kim, Woong Bin; Yoon, Bo Eun; Shen, Feng Yan; Lee, Seung Won; Soong, Tuck Wah; Han, Hee Chul; Colwell, Christopher S.; Lee, Changjoon; Kim, Yang In.

In: European Journal of Neuroscience, 2015.

Research output: Contribution to journalArticle

Kim, Yoon Sik ; Kim, Young Beom ; Kim, Woong Bin ; Yoon, Bo Eun ; Shen, Feng Yan ; Lee, Seung Won ; Soong, Tuck Wah ; Han, Hee Chul ; Colwell, Christopher S. ; Lee, Changjoon ; Kim, Yang In. / Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-Ca<inf>V</inf>1.3-RyR pathway in the mouse. In: European Journal of Neuroscience. 2015.
@article{e5158219981d438291e22cc00b8b4bd0,
title = "Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-CaV1.3-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, Ca2+-imaging techniques were used to demonstrate that histamine increases intracellular Ca2+ concentration ([Ca2+]i) in acutely dissociated SCN neurons and that this increase is blocked by the H1 histamine receptor (H1R) antagonist pyrilamine, the removal of extracellular Ca2+ and the L-type Ca2+ channel blocker nimodipine. The histamine-induced Ca2+ transient is reduced, but not blocked, by application of the ryanodine receptor (RyR) blocker dantrolene. Immunohistochemical techniques indicated that CaV1.3 L-type Ca2+ channels are expressed mainly in the somata of SCN cells along with the H1R, whereas CaV1.2 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 CaV1.3 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 [Ca2+]i in SCN neurons by activating CaV1.3 channels through H1R, and secondarily by causing Ca2+-induced Ca2+ release from RyR-mediated internal stores.",
keywords = "Brain slice, Calcium, Dantrolene, Electrophysiology, Nimodipine",
author = "Kim, {Yoon Sik} and Kim, {Young Beom} and Kim, {Woong Bin} and Yoon, {Bo Eun} and Shen, {Feng Yan} and Lee, {Seung Won} and Soong, {Tuck Wah} and Han, {Hee Chul} and Colwell, {Christopher S.} and Changjoon Lee and Kim, {Yang In}",
year = "2015",
doi = "10.1111/ejn.13030",
language = "English",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-CaV1.3-RyR pathway in the mouse

AU - Kim, Yoon Sik

AU - Kim, Young Beom

AU - Kim, Woong Bin

AU - Yoon, Bo Eun

AU - Shen, Feng Yan

AU - Lee, Seung Won

AU - Soong, Tuck Wah

AU - Han, Hee Chul

AU - Colwell, Christopher S.

AU - Lee, Changjoon

AU - Kim, Yang In

PY - 2015

Y1 - 2015

N2 - 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, Ca2+-imaging techniques were used to demonstrate that histamine increases intracellular Ca2+ concentration ([Ca2+]i) in acutely dissociated SCN neurons and that this increase is blocked by the H1 histamine receptor (H1R) antagonist pyrilamine, the removal of extracellular Ca2+ and the L-type Ca2+ channel blocker nimodipine. The histamine-induced Ca2+ transient is reduced, but not blocked, by application of the ryanodine receptor (RyR) blocker dantrolene. Immunohistochemical techniques indicated that CaV1.3 L-type Ca2+ channels are expressed mainly in the somata of SCN cells along with the H1R, whereas CaV1.2 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 CaV1.3 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 [Ca2+]i in SCN neurons by activating CaV1.3 channels through H1R, and secondarily by causing Ca2+-induced Ca2+ release from RyR-mediated internal stores.

AB - 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, Ca2+-imaging techniques were used to demonstrate that histamine increases intracellular Ca2+ concentration ([Ca2+]i) in acutely dissociated SCN neurons and that this increase is blocked by the H1 histamine receptor (H1R) antagonist pyrilamine, the removal of extracellular Ca2+ and the L-type Ca2+ channel blocker nimodipine. The histamine-induced Ca2+ transient is reduced, but not blocked, by application of the ryanodine receptor (RyR) blocker dantrolene. Immunohistochemical techniques indicated that CaV1.3 L-type Ca2+ channels are expressed mainly in the somata of SCN cells along with the H1R, whereas CaV1.2 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 CaV1.3 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 [Ca2+]i in SCN neurons by activating CaV1.3 channels through H1R, and secondarily by causing Ca2+-induced Ca2+ release from RyR-mediated internal stores.

KW - Brain slice

KW - Calcium

KW - Dantrolene

KW - Electrophysiology

KW - Nimodipine

UR - http://www.scopus.com/inward/record.url?scp=84939839504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939839504&partnerID=8YFLogxK

U2 - 10.1111/ejn.13030

DO - 10.1111/ejn.13030

M3 - Article

C2 - 26215659

AN - SCOPUS:84942984677

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

ER -