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In cell biology, potassium channels are the most common type of ion channel. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cells, and control the electrical excitability of the cell membrane. In neurons, they shape action potentials and set the resting membrane potential. They regulate cellular processes such as the secretion of hormones, so their malfunction can lead to diseases.
Some potassium channels are voltage-gated ion channels that open or close in response to changes in the transmembrane voltage. They can also open in response to the presence of calcium ions or other signalling molecules. Others are constitutively open or possess high basal activation, such as the resting potassium channels that set the negative membrane potential of neurons. When open, they allow potassium ions to cross the membrane at a rate which is nearly as fast as their diffusion through bulk water. There are over 80 mammalian genes that encode potassium channel subunits. The pore-forming subunits of potassium channels have a homo- or heterotetrameric arrangement. Four subunits are arranged around a central pore. All potassium channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium selectivity.
Potassium channels found in bacteria are amongst the most studied of ion channels, in terms of their molecular structure. Using X-ray crystallography, profound insights have been gained into how potassium ions pass through these channels and why (smaller) sodium ions do not (since sodium ions have greater charge density, they have a larger shell of water molecules surrounding them and thus are more bulky). The 2003 Nobel Prize for Chemistry was awarded to Rod MacKinnon for his pioneering work on this subject.
Voltage sensitive channels
The voltage-gated K+ channels that provide the outward currents of action potentials have similarities to bacterial K+ channels. These channels have been studied by X-ray diffraction, allowing determination of structural features at atomic resolution. The function of these channels is explored by electrophysiological studies. Genetic approaches include screening for behavioral changes in animals with mutations in K+ channel genes. Such genetic methods allowed the genetic identification of the "Shaker" K+ channel gene in Drosophila before ion channel gene sequences were well known. Study of the altered properties of voltage-gated K+ channel proteins produced by mutated genes has helped reveal the functional roles of K+ channel protein domains and even individual amino acids within their structures.
Voltage-gated K+ channels of vertebrates typically have four protein subunits arranged as a ring, each contributing to the wall of the trans-membrane K+ pore. There are six major α-helical sequences in each subunit. Some of these are hydrophobic transmembrane sequences.
Voltage-gated K+ channels are selective for K+ over other cations such as Na+. There is a selectivity filter at the narrowest part of the transmembrane pore. Channel mutation studies revealed the parts of the subunits that are essential for ion selectivity. They include the amino acid sequence (Thr-Val-Gly-Tyr-Gly) or (Thr-Val-Gly-Phe-Gly) typical to the selectivity filter of voltage-gated K+ channels. As K+ passes through the pore, interactions between potassium ions and water molecules are prevented and the K+ interacts with specific atomic components of the Thr-Val-Gly-X-Gly sequences from the four channel subunits*.
Attempts continue to relate the structure of the mammalian voltage-gated K+ channel to its ability to respond to the voltage that exists across the membrane*. Specific domains of the channel subunits have been identified that are important for voltage-sensing and converting between the open conformation of the channel and closed conformations. There are at least two closed conformations; in one, the channel can open if the membrane potential becomes positive inside. Voltage-gated K+ channels inactivate after opening, entering a distinctive, second closed conformation. In the inactivated conformation, the channel cannot open, even if the transmembrane voltage is favorable. A domain at one end of the K+ channel protein mediates inactivation. This end of the protein can transiently plug the inner opening of the pore, preventing ion movement through the channel.
See also
External link
Reference
- Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science, 4th ed. McGraw-Hill, New York (2000). ISBN 0838577016
"Potassium channel"