Aquaporins: The renal water channels

Water is the most abundant molecule in any cell. Specialized membrane channel, proteins called aquaporins, facilitate water transport across cell membranes. At least seven aquaporins (AQP): 1, 2, 3, 4, 6, 7, and 11 are expressed in the kidneys. Aquaporins play a role in both the short-term and long-term regulation of water balance as well as in the pathophysiology of water balance disorders. Aquaporin is composed of a single peptide chain consisting of approximately 270 amino acids. Inherited central and nephrogenic diabetes insipidus are primarily due to the decreased expression of AQP2 while mutation in the AQP2 molecule is responsible for inherited central diabetes insipidus. In acquired causes of nephrogenic diabetes insipidus, there is a downregulation of AQP2 expression in the inner medulla of the kidney. Nephrotic syndrome is characterized by excessive sodium and water reabsorption, although in spite of this, patients do not develop hyponatremia. There is a marked downregulation of both AQP2 and AQP3 expression, which could be a physiologic response to extracellular water reabsorption in patients with nephrotic syndrome. There are some conditions in which aquaporin expression has been found to increase such as experimentally induced heart failure, cirrhosis, and pregnancy. Some drugs such as cisplatin and cyclosporine, also alter the expression of aquaporins. The three-pore model of peritoneal transport depicts the importance of aquaporins. Thus, the understanding of renal water channels has solved the mystery behind many water balance disorders. Further insights into the molecular structure and biology of aquaporins will help to lay a foundation for the development of future drugs.