CIRCADIAN REGULATION OF ELECTROLYTE AND WATER TRANSPORT IN THE RAT KIDNEY

Circadian oscillations have been reported in major renal functions such as renal blood flow, glomerular filtration rate, and urinary excretion. These oscillations can be explained, in part, by the rhythmic variations in renal transporter expressions. However, given that a multitude of renal transporters are regulated by the circadian clock, and that the functions of some of these transporters are coupled, the underlying mechanisms that link variations in transporter expression to the observed changes in kidney function have yet to be fully elucidated. To better understand the impact of the circadian clock on renal solute and water transport, we have developed a computational model of the epithelial transport of the rat kidney that represents the observed rhythmic variations in glomerular filtration rate (GFR) and in the activities of Na+/H+ exchanger 3, sodium-gLucose cotransporter 1, epithelial Na+ channels, pendrin, and renal outer-medullary K+ channels. The model predicts the rhythmic oscillations in GFR and key renal transporter activities give rise to a significant shift in transport loads among different nephron segments. Together, these oscillations yield 3-4-fold daily fluctuations in urine output and urinary electrolyte excretion rates.