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Circadian coordination of ATP release in the urothelium via connexin43 hemichannels
- Source :
- Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
- Publication Year :
- 2017
-
Abstract
- Day-night changes in the storage capacity of the urinary bladder are indispensable for sound sleep. Connexin 43 (Cx43), a major gap junction protein, forms hemichannels as a pathway of ATP in other cell types, and the urinary bladder utilizes ATP as a mechanotransduction signals to modulate its capacity. Here, we demonstrate that the circadian clock of the urothelium regulates diurnal ATP release through Cx43 hemichannels. Cx43 was expressed in human and mouse urothelium, and clock genes oscillated in the mouse urothelium accompanied by daily cycles in the expression of Cx43 and extracellular ATP release into the bladder lumen. Equivalent chronological changes in Cx43 and ATP were observed in immortalized human urothelial cells, but these diurnal changes were lost in both arrhythmic Bmal1-knockout mice and in BMAL1-knockdown urothelial cells. ATP release was increased by Cx43 overexpression and was decreased in Cx43 knockdown or in the presence of a selective Cx43 hemichannel blocker, which indicated that Cx43 hemichannels are considered part of the components regulating ATP release in the urothelium. Thus, a functional circadian rhythm exists in the urothelium, and coordinates Cx43 expression and function as hemichannels that provide a direct pathway of ATP release for mechanotransduction and signalling in the urothelium.
- Subjects :
- 0301 basic medicine
Cell type
Circadian clock
lcsh:Medicine
Connexin
urologic and male genital diseases
Article
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Mice
Adenosine Triphosphate
Animals
Humans
Circadian rhythm
Mechanotransduction
Urothelium
lcsh:Science
Aged
Multidisciplinary
lcsh:R
ARNTL Transcription Factors
female genital diseases and pregnancy complications
Cell biology
Circadian Rhythm
CLOCK
Mice, Inbred C57BL
030104 developmental biology
chemistry
Connexin 43
cardiovascular system
lcsh:Q
Female
sense organs
biological phenomena, cell phenomena, and immunity
Adenosine triphosphate
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....17587d88ad07991925f0490a86b9696a