Involvement of urinary bladder Connexin43and the circadian clock in coordinationof diurnal micturition rhythm

摘要

Nocturnal enuresis in children and nocturia in the elderly are two highly prevalent clinicalconditions characterized by a mismatch between urine production rate in the kidneys andstorage in the urinary bladder during the sleep phase. Here we demonstrate, using a novel methodfor automated recording of mouse micturition, that connexin43, a bladder gap junction protein,is a negative regulator of functional bladder capacity. Bladder connexin43 levels and functionalcapacity show circadian oscillations in wild-type mice, but such rhythms are completely lostin Cry-null mice having a dysfunctional biological clock. Bladder muscle cells have an internalclock, and show oscillations of connexin43 and gap junction function. A clock regulator, Reverbα, upregulates connexin43 transcription as a cofactor of sp1, using sp1 cis-elements of thepromoter. Therefore, circadian oscillation of connexin43 is associated with the biological clockand contributes to diurnal changes in bladder capacity, which avoids disturbance of sleep bymicturition.