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

• DOI: 10.1038/ncomms1812
• Publication Date: 2012-05-01T15:09:04Z
• Authors: Hiromitsu Negoro; Akihiro Kanematsu; Masao Doi; Sylvia O. Suadicani; Masahiro Matsuo; Masaaki Imamura; Takeshi Okinami; Nobuyuki Nishikawa; Tomonori Oura; Shigeyuki Matsui; Kazuyuki Seo; Motomi Tainaka; Shoichi Urabe; Emi Kiyokage; Takeshi Todo; Hitoshi Okamura; Yasuhiko Tabata; Osamu Ogawa
• Keywords: Nocturia; Urination; Master regulator

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.