Potassium channel 1011474 223391572 2008-07-03T21:46:40Z DOI bot 6652755 Citation maintenance. Removed redundant parameters. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. [[Image:Potassium channel1.png|thumb|250px|Top view of purple potassium ions moving through potassium channel ({{PDB|1BL8}})]] [[Image:Potassium channels shut and open.png|thumb|250px|Bacterial potassium channels shut (left, {{PDB|1k4c}}) and open (right, {{PDB2|1lnq}}). They can sense voltage differences across membrane, and then change conformation. For more details, see {{cite web |author= Dutta S, Goodsell DS |title=Potassium channels |publisher=RCSB Protein Data Bank |date=[[2005-04-30]] |work=Molecule of the Month |url=http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb38_1.html |accessdate=2007-10-13 }}]] 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.<ref name="pmid10798390">{{cite journal | author = Littleton JT, Ganetzky B | title = Ion channels and synaptic organization: analysis of the Drosophila genome | journal = Neuron | volume = 26 | issue = 1 | pages = 35–43 | year = 2000 | pmid = 10798390 | doi = 10.1016/S0896-6273(00)81135-6 }}</ref> They form [[potassium]]-selective [[ion channel pore|pore]]s that span [[cell membrane]]s. Furthermore potassium channels are found in most [[cell (biology)|cell]] types and control a wide variety of cell functions.<ref name="isbn0-87893-321-2">{{cite book | author = Hille, Bertil | title = Ion channels of excitable membranes | publisher = Sinauer | location = Sunderland, Mass | year = 2001 | chapter = Chapter 5: Potassium Channels and Chloride Channels | pages = pages 131-168 | isbn = 0-87893-321-2 | oclc = | doi = }}</ref><ref name="isbn0-8385-7701-6">{{cite book | author = Jessell, Thomas M.; [[Eric R. Kandel|Kandel, Eric R.]]; Schwartz, James H. | title = [[Principles of Neural Science]] | publisher = McGraw-Hill | location = New York | year = 2000 | edition = 4th edition | chapter = Chapter 6: Ion Channels | pages = pages 105-124 | isbn = 0-8385-7701-6 | oclc = | doi = }}</ref> ==Function== In excitable cells such as [[neuron]]s, they shape [[action potential]]s and set the [[resting potential|resting membrane potential]]. By contributing to the regulation of the [[cardiac action potential|action potential]] duration in [[cardiac muscle]], malfunction of potassium channels may cause life-threatening [[Cardiac arrhythmia|arrhythmias]]. They also regulate cellular processes such as the secretion of [[hormones]] (''e.g.'', [[insulin]] release from [[beta cell|beta-cells]] in the [[pancreas]]) so their malfunction can lead to diseases (such as [[Diabetes mellitus type 2|diabetes]]). ==Types== There are four major classes of potassium channels: * [[Calcium-activated potassium channel]] - open in response to the presence of [[calcium]] ions or other signalling molecules. * [[Inward-rectifier potassium ion channel|Inwardly rectifying potassium channel]] - passes current (positive charge) more easily in the inward direction (into the cell). * [[Tandem pore domain potassium channel]] - are constitutively open or possess high basal activation, such as the "resting potassium channels" or "leak 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]]. * [[Voltage-gated potassium channel]] - are [[voltage-gated ion channel]]s that open or close in response to changes in the [[membrane potential|transmembrane]] [[voltage]]. 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). {| class="wikitable" |+Potassium channel classes, function, and pharmacology.<ref name=Rang60>{{cite book | author=Rang, HP | title = Pharmacology | publisher = Churchill Livingstone | location = Edinburgh | year = 2003 | pages = page 60 | isbn = 0-443-07145-4 | oclc = | doi = }}</ref> |- |'''Class''' ! Subclasses !Function !Blockers !Activators |- | [[Calcium-activated potassium channel|Calcium-activated]] <BR> 6[[transmembrane helix|T]] & 1[[pore-forming loop|P]] | * [[BK channel]] * [[SK channel]] | * inhibition following stimuli increasing intracellular calcium | * [[apamin]] * [[charybdotoxin]] | * none |- |rowspan=3 | [[Inward-rectifier potassium ion channel|Inwardly rectifying]] <BR> 2[[transmembrane helix|T]] & 1[[pore-forming loop|P]] | * [[ROMK]] (K<sub>ir</sub>1.1) | * recycling and secretion of potassium in [[nephron]]s | * Nonselective: Ba<sup>2+</sup>, Cs<sup>+</sup> | * none |- | * [[G protein-coupled inwardly-rectifying potassium channel|GPCR regulated]] (K<sub>ir</sub>3.x) | * mediate the inhibitory effect of many [[GPCR]]s | * [[GPCR]] antagonists * [[ifenprodil]]<ref name="pmid16123769">{{cite journal | author = Kobayashi T, Washiyama K, Ikeda K | title = Inhibition of G protein-activated inwardly rectifying K+ channels by ifenprodil | journal = Neuropsychopharmacology | volume = 31 | issue = 3 | pages = 516–24 | year = 2006 | pmid = 16123769 | doi = 10.1038/sj.npp.1300844 }}</ref> | * [[GPCR]] agonists |- | * [[ATP-sensitive K+ channels|ATP-sensitive]] (K<sub>ir</sub>6.x) | * close when [[adenosine triphosphate|ATP]] is high to promote [[insulin]] secretion | * [[glibenclamide]] * [[tolbutamide]] | * [[diazoxide]] * [[pinacidil]] |- | [[Tandem pore domain potassium channel|Tandem pore domain]] <BR> 4[[transmembrane helix|T]] & 2[[pore-forming loop|P]] | * [[KCNK1|TWIK]] * [[KCNK4|TRAAK]] * [[KCNK2|TREK]] * [[KCNK3|TASK]] | * Contribute to [[resting potential]] | * none | * [[halothane]] |- | [[Voltage-gated potassium channel|Voltage-gated]] <BR> 6[[transmembrane helix|T]] & 1[[pore-forming loop|P]] | * [[hERG]] (K<sub>v</sub>11.1) * [[KvLQT1]] (K<sub>v</sub>7.1) | * [[action potential]] [[repolarization]] * limits frequency of action potentials (disturbances cause [[dysrhythmia]]) | * [[tetraethylammonium]] * [[4-aminopyridine]] * [[dendrotoxin]]s (some types) | * none |- |} ==Structure== [[Image:2r9r opm.gif|thumb|250px|Potassium channel KvAP, structure in a membrane-like environment. Calculated hydrocarbon boundaries of the [[lipid bilayer]] are indicated by red and blue dots.]] Potassium channels have a [[tetramer]]ic structure in which four identical protein [[subunit]]s associate to form a four fold [[symmetry|symmetric]] ([[Symmetry_group#Two_dimensions|C<sub>4</sub>]]) 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 C<sub>4</sub> 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 [[subunit]]s. However potassium channels found in [[bacterium|bacteria]] are amongst the most studied of ion channels, in terms of their molecular structure. Using [[X-ray crystallography]],<ref name="pmid9525859">{{cite journal | author = Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R | title = The structure of the potassium channel: molecular basis of K<sup>+</sup> conduction and selectivity | journal = Science | volume = 280 | issue = 5360 | pages = 69–77 | year = 1998 | pmid = 9525859 | doi = 10.1126/science.280.5360.69 }}</ref><ref name="pmid9525854">{{cite journal | author = MacKinnon R, Cohen SL, Kuo A, Lee A, Chait BT | title = Structural conservation in prokaryotic and eukaryotic potassium channels | journal = Science | volume = 280 | issue = 5360 | pages = 106–9 | year = 1998 | pmid = 9525854 | doi = 10.1126/science.280.5360.106 }}</ref> 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]] [[molecule]]s surrounding them and thus are more bulky).<ref name="pmid9556453">{{cite journal | author = Armstrong C | title = The vision of the pore | journal = Science | volume = 280 | issue = 5360 | pages = 56–7 | year = 1998 | pmid = 9556453 | doi = 10.1126/science.280.5360.56 }}</ref> The [[2003]] [[Nobel Prize for Chemistry]] was awarded to [[Roderick MacKinnon|Rod MacKinnon]] for his pioneering work in this area.<ref name="Nobel_Prize_2003">{{cite web | url = http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/ | title = The Nobel Prize in Chemistry 2003 | accessdate = 2007-11-16 | publisher = The Nobel Foundation }}</ref> ==Selectivity filter== [[Image:1K4C.png|thumb|250px|'''Crystallographic structure of the bacterial KcsA potassium channel ({{PDB|1K4C}}).'''<ref name="pmid11689936">{{cite journal | author = Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R | title = Chemistry of ion coordination and hydration revealed by a K<sup>+</sup> channel-Fab complex at 2.0 Â resolution | journal = Nature | volume = 414 | issue = 6859 | pages = 43–8 | year = 2001 | pmid = 11689936 | doi = 10.1038/35102009 }}</ref> 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.]] 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.<ref name="pmid16253415">{{cite journal |author=Hellgren M, Sandberg L, Edholm O |title=A comparison between two prokaryotic potassium channels (K<sub>ir</sub>Bac1.1 and KcsA) in a molecular dynamics (MD) simulation study |journal=Biophys. Chem. |volume=120 |issue=1 |pages=1–9 |year=2006 |pmid=16253415 |doi=10.1016/j.bpc.2005.10.002}}</ref> 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 2<sup>4</sup>=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, S<sub>ext</sub> and S<sub>0</sub>, 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 S<sub>0</sub> and S<sub>ext</sub> 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.<ref name="pmid16253415">{{cite journal |author=Hellgren M, Sandberg L, Edholm O |title=A comparison between two prokaryotic potassium channels (K<sub>ir</sub>Bac1.1 and KcsA) in a molecular dynamics (MD) simulation study |journal=Biophys. Chem. |volume=120 |issue=1 |pages=1–9 |year=2006 |pmid=16253415 |doi=10.1016/j.bpc.2005.10.002}}</ref> ==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. ==Blockers== 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== <!--Muscarinic potassium channel redirects here--> ''See also [[G protein-coupled inwardly-rectifying potassium channel]]''<br /><br /> Some types of potassium channels are activated by [[muscarinic receptor]]s and these are called ''muscarinic potassium channels'' (I<sub>KACh</sub>). These channels are a heterotetramer comprised of two [[KCNJ3|GIRK1]] and two [[KCNJ5|GIRK4]] subunits.<ref name="pmid7877685">{{cite journal | author = Krapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE | title = The G-protein-gated atrial K<sup>+</sup> channel I<sub>KACh</sub> is a heteromultimer of two inwardly rectifying K<sup>+</sup>-channel proteins | journal = Nature | volume = 374 | issue = 6518 | pages = 135–41 | year = 1995 | pmid = 7877685 | doi = 10.1038/374135a0 }}</ref><ref name="pmid9478984">{{cite journal | author = Corey S, Krapivinsky G, Krapivinsky L, Clapham DE | title = Number and stoichiometry of subunits in the native atrial G-protein-gated K<sup>+</sup> channel, I<sub>KACh</sub> | journal = J. Biol. Chem. | volume = 273 | issue = 9 | pages = 5271–8 | year = 1998 | pmid = 9478984 | doi = 10.1074/jbc.273.9.5271 }}</ref> Examples are potassium channels in the heart, which, when activated by [[parasympathetic]] signals through [[M2 receptors|M2 muscarinic receptors]], causes an outward current of potassium which slows down the [[heart rate]].<ref name="pmid8521474">{{cite journal | author = Kunkel MT, Peralta EG | title = Identification of domains conferring G protein regulation on inward rectifier potassium channels | journal = Cell | volume = 83 | issue = 3 | pages = 443–9 | year = 1995 | pmid = 8521474 | doi = 10.1016/0092-8674(95)90122-1 }}</ref><ref name="pmid10414308">{{cite journal | author = Wickman K, Krapivinsky G, Corey S, Kennedy M, Nemec J, Medina I, Clapham DE | title = Structure, G protein activation, and functional relevance of the cardiac G protein-gated K<sup>+</sup> channel, I<sub>KACh</sub> | journal = Ann. N. Y. Acad. Sci. | volume = 868 | issue = | pages = 386–98 | year = 1999 | pmid = 10414308 | doi = | issn = | url = http://www.annalsnyas.org/cgi/content/abstract/868/1/386 }}</ref> ==See also== * [[Sodium ion channel]] == References == {{Reflist|2}} ==External links== * {{MeshName|Potassium+Channels}} * {{cite web | url = http://neuromuscular.wustl.edu/mother/chan.html#k | title = Potassium Channels | accessdate = 2008-03-10 | author = Neuromuscular Disease Center | authorlink = | coauthors = | date = 2008-03-04 | format = | work = | publisher = [[Washington University in St. Louis]] | pages = | language = | archiveurl = | archivedate = | quote = }} * {{UMichOPM|families|superfamily|8}} {{Ion channels}} [[Category:Ion channels]] [[Category:Electrophysiology]] [[Category:Integral membrane proteins]] [[de:Kaliumkanal]] [[ja:カリウムチャネル]]