Urothelium-specific deletion of connexin43 in the mouse urinary bladder alters distension-induced atp release and voiding behavior

Jin Kono, Masakatsu Ueda, Atsushi Sengiku, Sylvia O. Suadicani, Osamu Ogawa, Hiromitsu Negoro

Research output: Contribution to journalArticlepeer-review

Abstract

Connexin43 (Cx43), the main gap junction and hemichannel forming protein in the urinary bladder, participates in the regulation of bladder motor and sensory functions and has been reported as an important modulator of day–night variations in functional bladder capacity. However, because Cx43 is expressed throughout the bladder, the actual role played by the detrusor and the urothelial Cx43 is still unknown. For this purpose, we generated urothelium-specific Cx43 knockout (uCx43KO) mice using Cre-LoxP system. We evaluated the day–night micturition pattern and the urothelial Cx43 hemichannel function of the uCx43KO mice by measuring luminal ATP release after bladder distention. In wild-type (WT) mice, distention-induced ATP release was elevated, and functional bladder capacity was decreased in the animals’ active phase (nighttime) when Cx43 expression was also high compared to levels measured in the sleep phase (daytime). These day–night differences in urothelial ATP release and functional bladder capacity were attenuated in uCx43KO mice that, in the active phase, displayed lower ATP release and higher functional bladder capacity than WT mice. These findings indicate that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals’ awake, active phase.

Original languageEnglish (US)
Article number1594
Pages (from-to)1-12
Number of pages12
JournalInternational Journal of Molecular Sciences
Volume22
Issue number4
DOIs
StatePublished - Feb 2021

Keywords

  • ATP
  • Connexin43
  • Gap junction
  • Hemichannel
  • Urothelium

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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