Potassium ChannelsFebruary 2003 Molecule of the Month by Shuchismita Dutta and David Goodsell
doi: 10.2210/rcsb_pdb/mom_2003_2 (PDF Version, ePub Version )
All living cells are surrounded by a membrane that separates the watery world inside from the environment outside. Membranes are effective barriers for small ions (as well as for large molecules like proteins and DNA), providing a novel opportunity: differences in ion levels may be used for rapid signaling. For instance, a cell can raise the level of potassium ions inside it. Then, at a moment's notice, potassium can be released through channels in the membrane, creating a large change in the potassium level that will be felt throughout the cell. This process is used in all types of cells - bacteria, plants and animals. Two common examples of ion channels at work are seen in muscle contraction (which is started by the release of calcium ions), and nerve signaling (which involves a complex flow of sodium and potassium ions).
Ion Channels in Nerve Signals
When you smell a flower and know that it is a rose, or touch a hot object and immediately pull your hand away, nerves from your nose and hands use the release of ions to send signals to your brain and relay back the appropriate response. Nerve cells ready themselves for sending a signal by concentrating potassium ions inside and selectively pumping sodium ions out. This creates a difference in electrical potential across the cell membrane. To send a signal, sodium channels along the nerve open, allowing sodium to enter and reducing the voltage across the membrane. Potassium channels then open, letting the potassium ions out and re-establishing the original voltage. Other channels and pumps later reset the distribution of sodium and potassium ions inside and outside the cell. By clever design, both of these channels are sensitive to the voltage across the membrane, opening when the voltage changes. So, when the channels are opened at one end of a nerve cell, the flow of ions there instantly triggers channels further down the membrane to open. The result is a wave of channels opening that rushes down the nerve cell, carrying the nerve signal to the end.
Potassium channels are designed to allow the flow of potassium ions across the membrane, but to block the flow of other ions--in particular, sodium ions. These channels are typically composed of two parts: the filter, which selects and allows potassium but not sodium to pass, and the gate, which opens and closes the channel based on environmental signals. The structure shown here, from PDB entry 1bl8, shows the filter portion of a bacterial potassium channel. It is comprised of four identical protein molecules that span the width of the membrane, forming a selective pore down the center. Potassium ions, shown in green, flow freely through it, at rates of up to one hundred million ions per second. But it is also remarkably selective--it allows only one sodium ion to pass for every ten thousand potassium ions. As shown on a later page, crystallographic structures of this channel show how this is accomplished.
Open and Shut
Hundreds of different ion channels are made by living cells, for a variety of different functions. These all have similar filters, shown at the top in these two examples, connected to specialized gating domains, shown at the bottom. The membrane is shown schematically with a gray stripe and only two of the four chains are shown in the selectivity filters, so that you can see the pore. The gating domains open and shut the channel based on different signals, such as voltage or the presence of key signaling molecules. Several structural mechanisms are used for opening and closing potassium channels. In the two simple bacterial channels shown here, protein domains connected to the channel are thought to twist the four chains of the channel. This can be clearly seen by comparing the "open" channel structure of PDB entry 1lnq on the right with the "closed" structure of PDB entry 1k4c on the left (the gating domain of this structure is taken from the low resolution structure in 1f6g). The more complex channels found in nerve cells, which open and close after sensing changes in the voltage across the membrane, are thought to include a small tethered ball of protein that floats over and physically blocks the pore. (Note: somewhat surprisingly, the crystal structure of the closed channel has several potassium ions in the channel, shown here in green, but the structure of the open channel was solved without potassium ions.)
A Poisonous Aside
Ion channels play a critical role in signaling by nerves, so any blockage of these channels can have serious effects. Scorpions take advantage of this to paralyze their prey. Scorpion venom includes a collection of powerful neurotoxins that bind to ion channels and block the flow of ions. The example shown here, charybdotoxin (PDB entry 2crd), attacks potassium channels and blocks their function in nerve signaling. The surface of the protein is covered with positively-charged amino acids, colored bright blue, that are thought to glue the toxin over the exposed mouth of the pore. These toxins are typically small, highly stable proteins. Charybdotoxin is only 37 amino acids long, but contains three disulfide linkages--two are seen here in bright yellow--that hold the protein in its proper poisonous shape.
Exploring the Structure
The remarkable ability of the potassium channel to pass only potassium ions is
accomplished by a selectivity filter at one end of the pore, as shown here from PDB
entry 1k4c. For clarity, only two of the four protein molecules, one either side of the
channel, are shown in a stick representation. The little green spheres are potassium
ions passing through the selectivity filter. Normally potassium ions float around encased
in a cushion of water, like the one at the bottom of the stack of ions. Notice that it is
surrounded by eight water molecules, shown as red spheres. In order to pass through
the selectivity filter, each potassium ion has to shed these water molecules. This is how
the selectivity filter works: the dimensions of the channel are designed to mimic this
shell of water. Protein oxygen atoms that line the pore (colored in red) are oriented
toward the center of the channel. Eight of these oxygen atoms surround each potassium
ion, and act as a perfect replacement for the normal layer of water molecules. During
transport, the ions march from one site to the next along the pore. Once the potassium
ions cross this filter, they are again enclosed by water molecules. Sodium ions, on the
other hand, are slightly smaller in size, so they fail to interact with the oxygen atoms
lining the pore wall. They are far more comfortable with their normal shell of water than
they are inside the pore, so they are not efficiently ferried across the membrane.
This illustration was created with RasMol. You can create similar pictures by clicking on the accession code above and choosing one of the options under View Structure. You will find that this PDB file is a little tricky: it includes only one of the four chains in the pore and also includes a large antibody fragment that is bound to the channel. However, the Structure Explorer page for 1k4c contains an image that toggles between the biological molecule and the asymmetric unit. It also contains download links for both the coordinates (under the "File" menu) as well as the images (under the "Visualize" menu) of the biological molecule.
You might also look at PDB entry 1bl8, which includes all four chains and several potassium ions, but not the water molecules.
Additional information on potassium channels
Yellen, G. (2002): The voltage-gated potassium channels and their relatives. Nature
419, pp. 35-42.
Minor Jr.,D.L. (2001): Potassium channels: life in the post-structural world. Current Opinion in Structural Biology 11, pp. 408-414.
© 2013 David Goodsell & RCSB Protein Data Bank