A Tale of Two Channels version 1.0

Phenomena: How Does Our Cell Membrane Transport Water and Ions? The 2003 Nobel Prize in Chemistry Maintaining water and ion homeostasis is critically important for cell form and function. Water and ion …was awarded to Peter Agre and Rod MacKinnon for their work on the water channel (aquaporin) and channels are implicated in several diseases associated with the kidneys, heart, lungs and brain. But how the potassium channel, respectively. While it was known for some time that cells contained pores for do they work? With the lipid bilayer being largely hydrophobic, how do cells e ciently and eectively the transport of water and ions, their structure, composition and mechanism remained a mystery until achieve the proper homeostasis of polar molecules like water and salt? Read on to nd out… the 1990s. The fascinating stories of these proteins are told here on this molecular story placemat.

Peter Agre & Aquaporin: The Case of the Exploding Frog Eggs! Rod MacKinnon & selectivity of the Potassium Channel The existence of water channels was predicted as early as the mid-1800s. However, Within the nervous system, cells communicate to one another through action it wouldn’t be until over 100 years later, while studying Rh blood group antigens, potentials. These signals are dependent on the movement of ions across the cell that the identity of the hypothesized water channel would be conrmed and membrane. The movement of potassium ions is essential for these communications. revealed by Agre and his team. Agre demonstrated the function of aquaporin by The structure of the potassium channel is specic to potassium ions through the comparing Xenopus oocytes with and without aquaporin. Those with aquaporin presence of the selectivity lter. This lter is composed of amino acids positioned in swelled signicantly in a such a way that the carbonyl oxygens can hypotonic solution… to the coordinate the potassium ion as it moves through point that the oocytes lysed. the membrane.

Figure 1. Comparing water Figure 5. Potassium ions in water outside the channel transport in Xenopus oocytes share the same distance with oxygen as they do kept in a hypotonic medium. The inside the channel, allowing them to pass with ease. Figure 3. The cell membrane is permeated by numerous pores or test oocytes with aquaporin On the other hand, smaller sodium ions have a channels; most of which are uniquely evolved for the exchange of swelled and lysed, while the shorter distance that makes them in compatible with only one specic ion or molecule. control oocytes did not. the oxygen in the channel.

Structure of Aquaporin Structure of the Potassium Channel To date, at least thirteen variants of aquaporin have been found in all organisms, The potassium channel is a trans-membrane protein that allows the movement of from bacteria to plants and animals. The aquaporin protein is characterized by six potassium ions through the cell membrane. This protein is made up of four membrane-spanning helices and two half helices that collectively form a channel identical subunits with a channel running through the center. Carbonyl oxygen allowing primarily water molecules to move through the largely hydrophobic atoms in the channel replace the water molecules that normally surround the phospholipid bilayer of the cell. Aquaporins usually form tetramers, with each hydrated potassium ion, allowing the ions to rapidly monomer dening a single pore. Two main constriction sites have been identied pass through the channel. The carbonyl oxygen atoms that facilitate potassium in the aquaporin channels. In the center of the pore, two conserved Asn-Pro-Ala movement are located on residues Thr75, Val76, Gly77, Tyr78, and Gly79. The motifs (NPA), with two asparagine side chains pointing into the pore, are located at potassium ion interacts simultaneously with four carbonyl oxygen atoms (one the end of two half helices. The dipoles of the half helices generate an electrostatic from each subunit), thereby stripping the potassium of water molecules as it barrier in the NPA region, which is essential in ensuring that water molecules and passes through the channel. Interestingly, although sodium ions are smaller than not protons in the form of hydronium ions pass through the channel. Close to the potassium ions, they are excluded from the channel because they can’t interact extracellular exit of the channel, the aromatic/arginine (ar/R) constriction region simultaneously with all four carbonyl oxygens. forms the narrowest part of the pore and is therefore assumed to be important in Figure 2. The aquaporin protein is channel selectivity. Figure 6. The structure of the Implications: Potassium channels are important in producing electrical signals characterized by six membrane potassium channel is a in the nervous system, as well as maintaining proper muscle and heart function. spanning helices and two half trans-membrane protein made of Better understanding ion channels like the potassium channels is also useful in Implications: Various aquaporin proteins are especially important in the kidneys, helices that collectively form a four identical subunits with a where 150-200 liters of water must be resorbed daily. Alterations in aquaporin channel allowing primarily water channel of carbonyl oxygens drug interaction and targeting studies. expression or function can be rate-limiting for water transport across membranes. molecules to move through the running through the center. The Ultimately, they could be a target for therapy in diseases of altered water largely hydrophobic phospholipid carbonyl oxygens replace water on Resources: bilayer of the cell. the potassium, allowing them to homeostasis such as diabetes insipidus, edema and glaucoma. Agre, Peter. The Aquaporin Water Channels. Proceedings of the American Thoracic Society. Vol 3, 5-13. 2006. rapidly pass through. Doyle, Declan. Et. al. The structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity. Science. 280, 69. 1998. The Nobel Prize Award, 2003. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2003/popular.html