A brief survey of aquaporins and their implications for renal physiology.

Abstract

Aquaporins (AQPs) are an important family of proteins that efficiently channel water through the cell membranes. Although water can diffuse across biological membranes at measurable rates, physiologists had long predicted the existence of channels to facilitate rapid reabsorption of water by renal tubular cells. With AQPs present, water can "gush" through the membrane at the extraordinary rate of three billion water molecules per second per aquaporin channel. In their absence, water only trickles across the hydrophobic lipid bilayers of cell membranes. Aquaporins have fascinated researchers over the last decade, culminating in the 2003 Nobel Prize for Chemistry given to their discoverer, Dr. Peter Agre. During the 1990s, scientists identified and characterized members of the mammalian aquaporin family, now designated as AQP0 through AQP10. AQPs are also found in many plant and bacterial species. However, their relevance to the clinical laboratory is only recently emerging. Dr. Agre's Nobel symposium address provides an excellent mini-review of aquaporins in medicine. Our understanding of renal physiology and pathophysiology has advanced greatly as we account for the subtle implications of various AQP systems. For example, nephrogenic diabetes insipidus (NDI), the inability to produce concentrated urine, can result from several different malfunctions in the AQP2 system controlled by anti-diuretic hormone (ADH). Virtually all mammalian cells incorporate aquaporins into their cell membranes, and many cells produce multiple aquaporins, each with a specific function. It is therefore not surprising that malfunctions have important clinical conditions. The present article discusses the implications of aquaporins for renal physiology, while the accompanying article is focused on the clinical aspects of aquaporins.