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Publication : The oscillation of intracellular Ca<sup>2+</sup> influx associated with the circadian expression of Piezo1 and TRPV4 in the bladder urothelium.

First Author  Ihara T Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  5699
PubMed ID  29632308 Mgi Jnum  J:263078
Mgi Id  MGI:6162845 Doi  10.1038/s41598-018-23115-w
Citation  Ihara T, et al. (2018) The oscillation of intracellular Ca(2+) influx associated with the circadian expression of Piezo1 and TRPV4 in the bladder urothelium. Sci Rep 8(1):5699
abstractText  We previously showed that bladder functions are controlled by clock genes with circadian rhythm. The sensation of bladder fullness (SBF) is sensed by mechano-sensor such as Piezo1 and TRPV4 in the mouse bladder urothelium. However, functional circadian rhythms of such mechano-sensors remain unknown. To investigate functional circadian changes of these mechano-sensors, we measured circadian changes in stretch-evoked intracellular Ca(2+) influx ([Ca(2+)] i ) using mouse primary cultured urothelial cells (MPCUCs). Using Ca(2+) imaging, stretch-evoked [Ca(2+)] i was quantified every 4 h in MPCUCs derived from wild-type (WT) and Clock (Delta19/Delta19) mice, which showed a nocturia phenotype. Furthermore, a Piezo1 inhibitor GsMTx4 and a TRPV4 inhibitor Ruthenium Red were applied and stretch-evoked [Ca(2+)] i in MPCUCs was measured to investigate their contribution to SBF. Stretch-evoked [Ca(2+)] i showed a circadian rhythm in the WT mice. In contrast, Clock (Delta19/Delta19) mice showed disrupted circadian rhythm. The administration of both GsMTx4 and Ruthenium Red eliminated the circadian rhythm of stretch-evoked [Ca(2+)] i in WT mice. We conclude that SBF may have a circadian rhythm, which is created by functional circadian changes of Piezo1 and TRPV4 being controlled by clock genes to be active during wakefulness and inactive during sleep. Abnormalities of clock genes disrupt SBF, and induce nocturia.
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