title: Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm.
abstract: 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-erbα, 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.
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto 606-8507, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Negoro
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kanematsu
authors.forename: Masao
authors.initials: M
authors.lastname: Doi
authors.forename: Sylvia O
authors.initials: SO
authors.lastname: Suadicani
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsuo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Imamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okinami
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nishikawa
authors.forename: Tomonori
authors.initials: T
authors.lastname: Oura
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Matsui
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Seo
authors.forename: Motomi
authors.initials: M
authors.lastname: Tainaka
authors.forename: Shoichi
authors.initials: S
authors.lastname: Urabe
authors.forename: Emi
authors.initials: E
authors.lastname: Kiyokage
authors.forename: Takeshi
authors.initials: T
authors.lastname: Todo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D057906:Circadian Clocks; D002940:Circadian Rhythm; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032342:Muscle Cells / Q000378:metabolism; D053158:Nocturia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D053206:Nocturnal Enuresis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D001743:Urinary Bladder / Q000378:metabolism* / Q000503:physiopathology; D014554:Urination
chemical_list: D018031:Connexin 43; D016329:Sp1 Transcription Factor