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In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms.[1] They form potassium-selective pores that span cell membranes. Furthermore potassium channels are found in most cell types and control a wide variety of cell functions.[2][3]


In excitable cells such as neurons, they shape action potentials and set the resting membrane potential.

By contributing to the regulation of the action potential duration in cardiac muscle, malfunction of potassium channels may cause life-threatening arrhythmias.

They also regulate cellular processes such as the secretion of hormones (e.g., insulin release from beta-cells in the pancreas) so their malfunction can lead to diseases (such as diabetes).


There are four major classes of potassium channels:

The following table contains a comparison of the major classes of potassium channels with representative examples (for a complete list of channels within each class, see the respective class pages).

Potassium channel classes, function, and pharmacology.[4]
Class Subclasses Function Blockers Activators
6T & 1P
  • inhibition following stimuli increasing intracellular calcium
  • none
Inwardly rectifying
2T & 1P
  • recycling and secretion of potassium in nephrons
  • Nonselective: Ba2+, Cs+
  • none
  • mediate the inhibitory effect of many GPCRs
  • close when ATP is low to promote insulin secretion
Tandem pore domain
4T & 2P
  • none
6T & 1P
  • none


Potassium channels have a tetrameric structure in which four identical protein subunits associate to form a four fold symmetric (C4) complex arranged around a central ion conducting pore (i.e., a homotetramer). Alternatively four related but not identical protein subunits may associate to form heterotetrameric complexes with pseudo C4 symmetry. All potassium channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium selective permeability.

There are over 80 mammalian genes that encode potassium channel subunits. However potassium channels found in bacteria are amongst the most studied of ion channels, in terms of their molecular structure. Using X-ray crystallography,[6][7] 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).[8] The 2003 Nobel Prize for Chemistry was awarded to Rod MacKinnon for his pioneering work in this area.[9]

Top view of purple potassium ions moving through potassium channel
Bacterial potassium channels shut (left) and open (right). They can sense voltage differences across membrane, and then change conformation. For more details, see Dutta S, Goodsell DS (2005-04-30). "Potassium channels". Molecule of the Month. RCSB Protein Data Bank. Retrieved 2007-10-13.
Potassium channel KvAP, structure in a membrane-like environment. Calculated hydrocarbon boundaries of the lipid bilayer are indicated by red and blue dots.
Crystallographic structure of the bacterial KcsA potassium channel (PDB: 1K4C​).[10] In this figure, only two of the four subunits of the tetramer are displayed for the sake of clarity. The protein is displayed as a green cartoon diagram. In addition backbone carbonyl groups and threonine sidechain protein atoms (oxygen = red, carbon = green) are displayed. Finally potassium ions (occupying the S2 and S4 sites) and the oxygen atoms of water molecules (S1 and S3) are depicted as purple and red spheres respectively.

Selectivity filter

Potassium ion channels remove the hydration shell from the ion when it enters the selectivity filter. The selectivity filter is formed by five residues (TVGYG-in prokaryotic species) in the P loop from each subunit which have their electro-negative carbonyl oxygen atoms aligned towards the centre of the filter pore and form an anti-prism similar to a water solvating shell around each potassium binding site. The distance between the carbonyl oxygens and potassium ions in the binding sites of the selectivity filter is the same as between water oxygens in the first hydration shell and a potassium ion in water solution. Passage of sodium ions would be energetically unfavorable since the strong interactions between the filter and pore helix would prevent the channel from collapsing to the smaller sodium ion size. The selectivity filter opens towards the extracellular solution, exposing four carbonyl oxygens in a glycine residue (Gly79 in KcsA). The next residue towards the extracellular side of the protein is the negatively charged Asp80 (KcsA). This residue together with the five filter residues form the pore that connects the water filled cavity in the centre of the protein with the extracellular solution.[11]

The carbonyl oxygens are strongly electro-negative and cation attractive. The filter can accommodate potassium ions at 4 sites usually labelled S1 to S4 starting at the extracellular side. In addition one ion can bind in the cavity at a site called SC or one or more ions at the extracellular side at more or less well defined sites called S0 or Sext. Several different occupancies of these sites are possible. Since the X-ray structures are averages over many molecules, it is, however, not possible to deduce the actual occupancies directly from such a structure. In general, there is some disadvantage due to electrostatic repulsion to have two neighbouring sites occupied by ions. The mechanism for ion translocation in KcsA has been studied extensively by simulation techniques. A complete map of the free energies of the 24=16 states (characterised by the occupancy of the S1, S2, S3 and S4 sites) has been calculated with molecular dynamics simulations resulting in the prediction of an ion conduction mechanism in which the two doubly occupied states (S1, S3) and (S2, S4) play an essential role. The two extracellular states, Sext and S0, were found in a better resolved structure of KcsA at high potassium concentration. In free energy calculations the entire ionic pathway from the cavity, through the four filter sites out to S0 and Sext was covered in MD simulations. The amino acids sequence of the selectivity filter of potassium ion channels is conserved with the exception that an isoleucine residue in eukaryotic potassium ion channels often is substituted with a valine residue in prokaryotic channels.[11]

Central Cavity

A 10 Å wide central pore is located near the center of the transmembrane channel where the energy barrier is highest for the transversing ion due to the hydrophobity of the channel wall. The water-filled cavity and the polar C-terminus of the pore helices ease the energetic barrier for the ion. Repulsion by preceding multiple potassium ions is thought to aid the throughput of the ions.


Potassium channel blockers, such as 4-Aminopyridine and 3,4-Diaminopyridine, have been investigated for the treatment of conditions such as multiple sclerosis.

Muscarinic potassium channel

See also G protein-coupled inwardly-rectifying potassium channel

Some types of potassium channels are activated by muscarinic receptors and these are called muscarinic potassium channels (IKACh). These channels are a heterotetramer comprised of two GIRK1 and two GIRK4 subunits.[12][13] Examples are potassium channels in the heart, which, when activated by parasympathetic signals through M2 muscarinic receptors, causes an inward current of potassium which slows down the heart rate.[14][15]

See also


  1. Littleton JT, Ganetzky B (2000). "Ion channels and synaptic organization: analysis of the Drosophila genome". Neuron. 26 (1): 35–43. doi:10.1016/S0896-6273(00)81135-6. PMID 10798390.
  2. Hille, Bertil (2001). "Chapter 5: Potassium Channels and Chloride Channels". Ion channels of excitable membranes. Sunderland, Mass: Sinauer. pp. pages 131-168. ISBN 0-87893-321-2.
  3. Jessell, Thomas M.; Kandel, Eric R.; Schwartz, James H. (2000). "Chapter 6: Ion Channels". Principles of Neural Science (4th edition ed.). New York: McGraw-Hill. pp. pages 105-124. ISBN 0-8385-7701-6.
  4. Rang, HP (2003). Pharmacology. Edinburgh: Churchill Livingstone. pp. page 60. ISBN 0-443-07145-4.
  5. Kobayashi T, Washiyama K, Ikeda K (2006). "Inhibition of G protein-activated inwardly rectifying K+ channels by ifenprodil". Neuropsychopharmacology. 31 (3): 516–24. doi:10.1038/sj.npp.1300844. PMID 16123769.
  6. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1998). "The structure of the potassium channel: molecular basis of K+ conduction and selectivity". Science. 280 (5360): 69–77. doi:10.1126/science.280.5360.69. PMID 9525859.
  7. MacKinnon R, Cohen SL, Kuo A, Lee A, Chait BT (1998). "Structural conservation in prokaryotic and eukaryotic potassium channels". Science. 280 (5360): 106–9. doi:10.1126/science.280.5360.106. PMID 9525854.
  8. Armstrong C (1998). "The vision of the pore". Science. 280 (5360): 56–7. doi:10.1126/science.280.5360.56. PMID 9556453.
  9. "The Nobel Prize in Chemistry 2003". The Nobel Foundation. Retrieved 2007-11-16.
  10. Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R (2001). "Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 Â resolution". Nature. 414 (6859): 43–8. doi:10.1038/35102009. PMID 11689936.
  11. 11.0 11.1 Hellgren M, Sandberg L, Edholm O (2006). "A comparison between two prokaryotic potassium channels (KirBac1.1 and KcsA) in a molecular dynamics (MD) simulation study". Biophys. Chem. 120 (1): 1–9. doi:10.1016/j.bpc.2005.10.002. PMID 16253415.
  12. Krapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE (1995). "The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+-channel proteins". Nature. 374 (6518): 135–41. doi:10.1038/374135a0. PMID 7877685.
  13. Corey S, Krapivinsky G, Krapivinsky L, Clapham DE (1998). "Number and stoichiometry of subunits in the native atrial G-protein-gated K+ channel, IKACh". J. Biol. Chem. 273 (9): 5271–8. doi:10.1074/jbc.273.9.5271. PMID 9478984.
  14. Kunkel MT, Peralta EG (1995). "Identification of domains conferring G protein regulation on inward rectifier potassium channels". Cell. 83 (3): 443–9. doi:10.1016/0092-8674(95)90122-1. PMID 8521474.
  15. Wickman K, Krapivinsky G, Corey S, Kennedy M, Nemec J, Medina I, Clapham DE (1999). "Structure, G protein activation, and functional relevance of the cardiac G protein-gated K+ channel, IKACh". Ann. N. Y. Acad. Sci. 868: 386–98. PMID 10414308.

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