Diurnal function and expression of aquaporins in the mouse kidney.

Abstract

Aquaporins (AQPs) are a family of water channels found throughout the body and in the kidney; they function in maintaining water homeostasis. The insertion of AQPs into the plasma membrane of the kidney cells drives water reabsorption back into the circulation, and the concentration of the urine involves AQP2 apical localization in the collecting duct principal cells. Kidney functions, like glomerular filtration rate (GFR) and urine flow, are significantly greater during the active period compared with the inactive period when sleeping. We hypothesized that there is a diurnal pattern in urine and/or plasma osmolality and that this reflects changes in kidney aquaporins in mice. Male and female C57BL/6J mice were studied in the middle of their active period [zeitgeber time (ZT) 18] or the middle of their inactive period (ZT6). We confirmed GFR was greater at ZT18 compared with ZT6. Urine and plasma osmolality were significantly greater at ZT18 in both sexes. Although ∼18% of kidney RNA had a diurnal pattern, the changes observed in the Aqp genes did not reflect protein abundance differences where nephron AQP1, AQP2, and AQP4 abundance were greater at ZT18 compared with ZT6. In conclusion, diurnal variability in plasma osmolality and urine-concentrating ability is likely driven by time-of-day changes in intake, greater GFR, and establishment of the medullary interstitial gradient during the active period. Greater nephron aquaporins in the middle of the active period may function to reabsorb water while the kidney excretes excess solutes to dilute the plasma osmolality and maintain fluid-electrolyte balance.NEW & NOTEWORTHY Mouse plasma and urine osmolalities are greater in the middle of the active period, when food/water intake, gut reabsorption, glomerular filtration rate, and urine flow are increased. There were time-of-day effects on aquaporin mRNA, and increased nephron abundance of aquaporins during the middle of the active period. As the kidneys excrete the excess solutes, the medullary interstitial gradient and aquaporins are primed to concentrate the urine and return the plasma osmolality to a steady state.