Diagenode

Histamine 1 receptor-Gβγ-cAMP/PKA-CFTR pathway mediates the histamine-induced resetting of the suprachiasmatic circadian clock


Yoon Sik Kim, Young-Beom Kim, Woong Bin Kim, Seung Won Lee, Seog Bae Oh, Hee-Chul Han, C. Justin LeeEmail author, Christopher S. Colwell and Yang In Kim

Background

Recent evidence indicates that histamine, acting on histamine 1 receptor (H1R), resets the circadian clock in the mouse suprachiasmatic nucleus (SCN) by increasing intracellular Ca2+ concentration ([Ca2+]i) through the activation of CaV1.3 L-type Ca2+ channels and Ca2+-induced Ca2+ release from ryanodine receptor-mediated internal stores.

Results

In the current study, we explored the underlying mechanisms with various techniques including Ca2+- and Cl-imaging and extracellular single-unit recording. Our hypothesis was that histamine causes Cl efflux through cystic fibrosis transmembrane conductance regulator (CFTR) to elicit membrane depolarization needed for the activation of CaV1.3 Ca2+ channels in SCN neurons. We found that histamine elicited Cl efflux and increased [Ca2+]i in dissociated mouse SCN cells. Both of these events were suppressed by bumetanide [Na+-K+-2Cl cotransporter isotype 1 (NKCC1) blocker], CFTRinh-172 (CFTR inhibitor), gallein (Gβγ protein inhibitor) and H89 [protein kinase A (PKA) inhibitor]. By itself, H1R activation with 2-pyridylethylamine increased the level of cAMP in the SCN and this regulation was prevented by gallein. Finally, histamine-evoked phase shifts of the circadian neural activity rhythm in the mouse SCN slice were blocked by bumetanide, CFTRinh-172, gallein or H89 and were not observed in NKCC1 or CFTR KO mice.

Conclusions

Taken together, these results indicate that histamine recruits the H1R-Gβγ-cAMP/PKA pathway in the SCN neurons to activate CaV1.3 channels through CFTR-mediated Cl efflux and ultimately to phase-shift the circadian clock. This pathway and NKCC1 may well be potential targets for agents designed to treat problems resulting from the disturbance of the circadian system.

Tags
Bioruptor
Article alert

Share this article

Published
March, 2016

Source

Related product

  • Bioruptor-pico-next-gen-sequencing
    B01060001
    Bioruptor® Pico sonication device
  • some alt
    B01020001
    Bioruptor® Plus sonication device

Events

  • Epigenetic Mechanisms in Health and Disease 2017
    Barcelona, Spain
    Oct 25-Oct 26, 2017
  • 35ème Congrès de la Societé Française de Toxicologie Génétique
    Marseille, France
    Oct 26-Oct 27, 2017
  • 7th Australian Epigenetics Conference
    Brisbane, Australia
    Oct 29-Nov 1, 2017
  • Australian Genomic Technologies Association (AGTA 2017 Annual Conference)
    Hobart, Tasmania
    Oct 29-Nov 1, 2017
 See all events

         Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics