Physiology and pathophysiology of renal aquaporins

The discovery of aquaporin membrane water channels by Agre and coworkers an swered a long-standing biophysical question of how water specifically cross es biologic membranes, and provided insight, at the molecular level, into t he fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to b e present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is extremely abundant in the proximal tubule and d escending thin limb, where it appears to provide the chief route for proxim al nephron water reabsorption. AQP2 is abundant in the collecting duct prin cipal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin-regulated tr afficking of AQP2 between an intracellular reservoir and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of AQP2 expression. Impor tantly, multiple studies have now identified a critical role of AQP2 in sev eral inherited and acquired water balance disorders. This concerns inherite d forms of nephrogenic diabetes insipidus and several, much more common acq uired types of nephrogenic diabetes insipidus where AQP2 expression and/or targeting are affected. Conversely, AQP2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. AQP3 and AQP3 are basolateral water channels loc ated in the kidney collecting duct, and AQP6 and AQP7 appear to be expresse d at lower abundance at several sites including the proximal tubule. This r eview focuses mainly on the role of AQP2 in water balance regulation and in the pathophysiology of water balance disorders.