Aquaporins: the Cell's Water Channels

Water moves in and out of cells by osmosis through the cell membrane. However, it was long suspected that there was an additional mechanism for moving water across the cell membrane. The 1992 discovery of aquaporins by Peter Agre, membrane proteins facilitating water transport in and out of cells, was deemed so important that Agre was awarded the 2003 Nobel Prize in Chemistry (together with Roderick MacKinnon for his discovery of ion channels). To date, 13 variants of aquaporins have been discovered in humans. A single human aquaporin transports water, one molecule at the time, at the rate of about 3 billion water molecules per second, in accordance with the prevailing osmotic gradient (the water moves in a direction away from a low and toward a high concentration of salt and nutritional substances). In doing so, aquaporins allow cells to regulate their volume and internal osmotic pressure.

Every cell membrane may contain thousands of such water channels. The water transport in and out of cells is key to a great number of physiological processes. For example, aquaporins are needed when water must be retrieved when urine is concentrated in the kidney.

Aquaporins selectively conduct water molecules in and out of cells, while preventing the passage of ions and other solutes. However, there are some variants of aquaporins that transport small amounts of uncharged solutes, such as glycerol, CO2, ammonia and urea across the cell membrane, depending on the size of the pore. All aquaporins are completely impermeable to charged species, such as protons.

Aquaporins and Disease

As aquaporins are essential to life, it is only to be expected that dysfunction of these membrane proteins may cause or contribute to disease. Aquaporins have been associated with critical water transport in the kidneys, lungs, and skeletal muscle. Further, aquaporins are part of the blood-brain barrier. They also influence the water content of the eyes, mouth, and skin.

Among the diseases linked to dusfunction of aquaporins are diabetes insipidus, salivary gland dysfunction (Sjogren's Syndrome), cataracts, and even hypertension. Although the cause of hypertension is multifactoral, a major role is played by the readsorption of too much water by the kidney. As a result, the majority of drugs used to treat hypertension today target the kidney so it loses excess water, which lowers blood pressure.

Fluid transport is a major function of the gastrointestinal (GI) tract with more than 9 litres of fluid being absorbed or secreted across epithelia in human salivary glands, stomach, the hepatobiliary tract, pancrease, small intestine and colon, it is believed that aquaporins play a role in several GI tract related diseases as well. At least seven aquaporins are expressed in various tissues of the GI tract.

Further, it is known that aquaporins play an important role in the regulation of epidermal water content. Changes in aquaporin-3 (AQP3) have been associated with eczema and spongiosis. In addition, the expression of AQP3 has been shown to be strongly affected by age and chronic sun exposure. This means SQPs are key targets to improve the resistance and quality of the skin surface as well as to improve aging and sun exposure induced dry areas. Substances targeting these AQPs could be used for both pharmaceutical and cosmetic products aimed to treat various skin conditions.

Read more about the discovery of aquaporins here.