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Publication : Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm.

First Author  Negoro H Year  2012
Journal  Nat Commun Volume  3
Pages  809 PubMed ID  22549838
Mgi Jnum  J:205637 Mgi Id  MGI:5545958
Doi  10.1038/ncomms1812 Citation  Negoro H, et al. (2012) Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm. Nat Commun 3:809
abstractText  Nocturnal enuresis in children and nocturia in the elderly are two highly prevalent clinical conditions characterized by a mismatch between urine production rate in the kidneys and storage in the urinary bladder during the sleep phase. Here we demonstrate, using a novel method for automated recording of mouse micturition, that connexin43, a bladder gap junction protein, is a negative regulator of functional bladder capacity. Bladder connexin43 levels and functional capacity show circadian oscillations in wild-type mice, but such rhythms are completely lost in Cry-null mice having a dysfunctional biological clock. Bladder muscle cells have an internal clock, and show oscillations of connexin43 and gap junction function. A clock regulator, Rev-erbalpha, upregulates connexin43 transcription as a cofactor of Sp1, using Sp1 cis-elements of the promoter. Therefore, circadian oscillation of connexin43 is associated with the biological clock and contributes to diurnal changes in bladder capacity, which avoids disturbance of sleep by micturition.
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