Potassium channel#Structure

Potassium channels function to conduct potassium ions down their electrochemical gradient, doing so both rapidly (up to the diffusion rate of K⁺ ions in bulk water) and selectively (excluding, most notably, sodium despite the sub-angstrom difference in ionic radius).{{cite book | vauthors = Lim C, Dudev T |chapter= Roles and Transport of Sodium and Potassium in Plants|publisher= Springer|date= 2016|series= Metal Ions in Life Sciences|volume=16| journal = The Alkali Metal Ions: Their Role in Life| veditors = Sigel A, Sigel H, Sigel RK | title = The Alkali Metal Ions: Their Role for Life |pages= 325–347|doi=10.1007/978-3-319-21756-7_9|pmid= 26860305 |isbn= 978-3-319-21755-0}} Biologically, these channels act to set or reset the resting potential in many cells. In excitable cells, such as neurons, the delayed counterflow of potassium ions shapes the action potential.

By contributing to the regulation of the cardiac action potential duration in cardiac muscle, malfunction of potassium channels may cause life-threatening arrhythmias. Potassium channels may also be involved in maintaining vascular tone.

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).

Some toxins, such as dendrotoxin, are potent because they block potassium channels.indirectly cited from reference number 3,4,5,6 in {{cite journal | vauthors = Rehm H, Lazdunski M | title = Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 13 | pages = 4919–4923 | date = July 1988 | pmid = 2455300 | pmc = 280549 | doi = 10.1073/pnas.85.13.4919 | doi-access = free | bibcode = 1988PNAS...85.4919R }}

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.
• 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.
• Voltage-gated potassium channel - are voltage-gated ion channels that open or close in response to changes in the 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).

For more examples of pharmacological modulators of potassium channels, see potassium channel blocker and potassium channel opener.

Image:Potassium channel1.pngPotassium channels have a tetrameric structure in which four identical protein subunits associate to form a fourfold 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,{{cite journal | vauthors = Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R | display-authors = 6 | title = The structure of the potassium channel: molecular basis of K+ conduction and selectivity | journal = Science | volume = 280 | issue = 5360 | pages = 69–77 | date = April 1998 | pmid = 9525859 | doi = 10.1126/science.280.5360.69 | bibcode = 1998Sci...280...69D }}{{cite journal | vauthors = 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 = 106–109 | date = April 1998 | pmid = 9525854 | doi = 10.1126/science.280.5360.106 | s2cid = 33907550 | bibcode = 1998Sci...280..106M }} profound insights have been gained into how potassium ions pass through these channels and why (smaller) sodium ions do not.{{cite journal | vauthors = Armstrong C | title = The vision of the pore | journal = Science | volume = 280 | issue = 5360 | pages = 56–57 | date = April 1998 | pmid = 9556453 | doi = 10.1126/science.280.5360.56 | s2cid = 35339674 }} The 2003 Nobel Prize for Chemistry was awarded to Rod MacKinnon for his pioneering work in this area.{{cite web | url = http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/ | title = The Nobel Prize in Chemistry 2003 | access-date = 2007-11-16 | publisher = The Nobel Foundation }}

Image:1K4C.png ({{PDB|1K4C}}).{{cite journal | vauthors = Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R | title = Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution | journal = Nature | volume = 414 | issue = 6859 | pages = 43–48 | date = November 2001 | pmid = 11689936 | doi = 10.1038/35102009 | s2cid = 205022645 | bibcode = 2001Natur.414...43Z }} 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 a five residue sequence, TVGYG, termed the signature sequence, within each of the four subunits. This signature sequence is within a loop between the pore helix and TM2/6, historically termed the P-loop. This signature sequence is highly conserved, with the exception that a valine residue in prokaryotic potassium channels is often substituted with an isoleucine residue in eukaryotic channels. This sequence adopts a unique main chain structure, structurally analogous to a nest protein structural motif. The four sets of electronegative carbonyl oxygen atoms are aligned toward the center of the filter pore and form a square antiprism 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, providing an energetically-favorable route for de-solvation of the ions. Sodium ions, however, are too small to fill the space between the carbonyl oxygen atoms. Thus, it is energetically favorable for sodium ions to remain bound with water molecules in the extracellular space, rather than to pass through the potassium-selective ion pore.{{cite book | vauthors = Lodish H, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin K | display-authors = 6 |title=Molecular Cell Biology |date=2016 |publisher=W. H. Freeman and Company |location=New York, NY |isbn=978-1-4641-8339-3 |page=499 |edition=8th }} This width appears to be maintained by hydrogen bonding and van der Waals forces within a sheet of aromatic amino acid residues surrounding the selectivity filter.{{cite journal | vauthors = Sauer DB, Zeng W, Raghunathan S, Jiang Y | title = Protein interactions central to stabilizing the K+ channel selectivity filter in a four-sited configuration for selective K+ permeation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 40 | pages = 16634–16639 | date = October 2011 | pmid = 21933962 | pmc = 3189067 | doi = 10.1073/pnas.1111688108 | doi-access = free | bibcode = 2011PNAS..10816634S }} The selectivity filter opens towards the extracellular solution, exposing four carbonyl oxygens in a glycine residue (Gly79 in KcsA). The next residue toward 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 center of the protein with the extracellular solution.

The mechanism of potassium channel selectivity remains under continued debate. 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 neighboring sites occupied by ions. Proposals for the mechanism of selectivity have been made based on molecular dynamics simulations,{{cite journal | vauthors = Noskov SY, Roux B | title = Importance of hydration and dynamics on the selectivity of the KcsA and NaK channels | journal = The Journal of General Physiology | volume = 129 | issue = 2 | pages = 135–143 | date = February 2007 | pmid = 17227917 | pmc = 2154357 | doi = 10.1085/jgp.200609633 }} toy models of ion binding,{{cite journal | vauthors = Noskov SY, Bernèche S, Roux B | title = Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands | journal = Nature | volume = 431 | issue = 7010 | pages = 830–834 | date = October 2004 | pmid = 15483608 | doi = 10.1038/nature02943 | s2cid = 4414885 | bibcode = 2004Natur.431..830N }} thermodynamic calculations,{{cite journal | vauthors = Varma S, Rempe SB | title = Tuning ion coordination architectures to enable selective partitioning | journal = Biophysical Journal | volume = 93 | issue = 4 | pages = 1093–1099 | date = August 2007 | pmid = 17513348 | pmc = 1929028 | doi = 10.1529/biophysj.107.107482 | arxiv = physics/0608180 | bibcode = 2007BpJ....93.1093V }} topological considerations,{{cite journal | vauthors = Thomas M, Jayatilaka D, Corry B | title = The predominant role of coordination number in potassium channel selectivity | journal = Biophysical Journal | volume = 93 | issue = 8 | pages = 2635–2643 | date = October 2007 | pmid = 17573427 | pmc = 1989715 | doi = 10.1529/biophysj.107.108167 | bibcode = 2007BpJ....93.2635T }}{{cite journal | vauthors = Bostick DL, Brooks CL | title = Selectivity in K+ channels is due to topological control of the permeant ion's coordinated state | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 22 | pages = 9260–9265 | date = May 2007 | pmid = 17519335 | pmc = 1890482 | doi = 10.1073/pnas.0700554104 | doi-access = free | bibcode = 2007PNAS..104.9260B }} and structural differences{{cite journal | vauthors = Derebe MG, Sauer DB, Zeng W, Alam A, Shi N, Jiang Y | title = Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 2 | pages = 598–602 | date = January 2011 | pmid = 21187421 | pmc = 3021048 | doi = 10.1073/pnas.1013636108 | doi-access = free | bibcode = 2011PNAS..108..598D }} between selective and non-selective channels.

The mechanism for ion translocation in KcsA has been studied extensively by theoretical calculations and simulation.{{cite journal | vauthors = Hellgren M, Sandberg L, Edholm O | title = A comparison between two prokaryotic potassium channels (KirBac1.1 and KcsA) in a molecular dynamics (MD) simulation study | journal = Biophysical Chemistry | volume = 120 | issue = 1 | pages = 1–9 | date = March 2006 | pmid = 16253415 | doi = 10.1016/j.bpc.2005.10.002 }}{{cite journal | vauthors = Morais-Cabral JH, Zhou Y, MacKinnon R | title = Energetic optimization of ion conduction rate by the K+ selectivity filter | journal = Nature | volume = 414 | issue = 6859 | pages = 37–42 | date = November 2001 | pmid = 11689935 | doi = 10.1038/35102000 | s2cid = 4429890 | bibcode = 2001Natur.414...37M }} The prediction of an ion conduction mechanism in which the two doubly occupied states (S1, S3) and (S2, S4) play an essential role has been affirmed by both techniques. Molecular dynamics (MD) simulations suggest the two extracellular states, S_ext and S₀, reflecting ions entering and leaving the filter, also are important actors in ion conduction.

This region neutralizes the environment around the potassium ion so that it is not attracted to any charges. In turn, it speeds up the reaction.

A central pore, 10 Å wide, 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.

The presence of the cavity can be understood intuitively as one of the channel's mechanisms for overcoming the dielectric barrier, or repulsion by the low-dielectric membrane, by keeping the K⁺ ion in a watery, high-dielectric environment.

Image:038-PotassiumChannels.tiff

The flux of ions through the potassium channel pore is regulated by two related processes, termed gating and inactivation. Gating is the opening or closing of the channel in response to stimuli, while inactivation is the rapid cessation of current from an open potassium channel and the suppression of the channel's ability to resume conducting. While both processes serve to regulate channel conductance, each process may be mediated by a number of mechanisms.

Generally, gating is thought to be mediated by additional structural domains which sense stimuli and in turn open the channel pore. These domains include the RCK domains of BK channels,{{cite journal | vauthors = Yuan P, Leonetti MD, Pico AR, Hsiung Y, MacKinnon R | title = Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution | journal = Science | volume = 329 | issue = 5988 | pages = 182–186 | date = July 2010 | pmid = 20508092 | pmc = 3022345 | doi = 10.1126/science.1190414 | bibcode = 2010Sci...329..182Y }}{{cite journal | vauthors = Wu Y, Yang Y, Ye S, Jiang Y | title = Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel | journal = Nature | volume = 466 | issue = 7304 | pages = 393–397 | date = July 2010 | pmid = 20574420 | pmc = 2910425 | doi = 10.1038/nature09252 | bibcode = 2010Natur.466..393W }}{{cite journal | vauthors = Jiang Y, Pico A, Cadene M, Chait BT, MacKinnon R | title = Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel | journal = Neuron | volume = 29 | issue = 3 | pages = 593–601 | date = March 2001 | pmid = 11301020 | doi = 10.1016/S0896-6273(01)00236-7 | s2cid = 17880955 | doi-access = free }} and voltage sensor domains of voltage gated K⁺ channels. These domains are thought to respond to the stimuli by physically opening the intracellular gate of the pore domain, thereby allowing potassium ions to traverse the membrane. Some channels have multiple regulatory domains or accessory proteins, which can act to modulate the response to stimulus. While the mechanisms continue to be debated, there are known structures of a number of these regulatory domains, including RCK domains of prokaryotic{{cite journal | vauthors = Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R | title = Crystal structure and mechanism of a calcium-gated potassium channel | journal = Nature | volume = 417 | issue = 6888 | pages = 515–522 | date = May 2002 | pmid = 12037559 | doi = 10.1038/417515a | s2cid = 205029269 | bibcode = 2002Natur.417..515J }}{{cite journal | vauthors = Kong C, Zeng W, Ye S, Chen L, Sauer DB, Lam Y, Derebe MG, Jiang Y | display-authors = 6 | title = Distinct gating mechanisms revealed by the structures of a multi-ligand gated K(+) channel | journal = eLife | volume = 1 | pages = e00184 | date = December 2012 | pmid = 23240087 | pmc = 3510474 | doi = 10.7554/eLife.00184 | doi-access = free }}{{cite journal | vauthors = Cao Y, Jin X, Huang H, Derebe MG, Levin EJ, Kabaleeswaran V, Pan Y, Punta M, Love J, Weng J, Quick M, Ye S, Kloss B, Bruni R, Martinez-Hackert E, Hendrickson WA, Rost B, Javitch JA, Rajashankar KR, Jiang Y, Zhou M | display-authors = 6 | title = Crystal structure of a potassium ion transporter, TrkH | journal = Nature | volume = 471 | issue = 7338 | pages = 336–340 | date = March 2011 | pmid = 21317882 | pmc = 3077569 | doi = 10.1038/nature09731 | bibcode = 2011Natur.471..336C }} and eukaryotic channels, pH gating domain of KcsA,{{cite journal | vauthors = Uysal S, Cuello LG, Cortes DM, Koide S, Kossiakoff AA, Perozo E | title = Mechanism of activation gating in the full-length KcsA K+ channel | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 29 | pages = 11896–11899 | date = July 2011 | pmid = 21730186 | pmc = 3141920 | doi = 10.1073/pnas.1105112108 | doi-access = free | bibcode = 2011PNAS..10811896U }} cyclic nucleotide gating domains,{{cite journal | vauthors = Clayton GM, Silverman WR, Heginbotham L, Morais-Cabral JH | title = Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel | journal = Cell | volume = 119 | issue = 5 | pages = 615–627 | date = November 2004 | pmid = 15550244 | doi = 10.1016/j.cell.2004.10.030 | s2cid = 14149494 | doi-access = free }} and voltage gated potassium channels.{{cite journal | vauthors = Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, MacKinnon R | title = X-ray structure of a voltage-dependent K+ channel | journal = Nature | volume = 423 | issue = 6935 | pages = 33–41 | date = May 2003 | pmid = 12721618 | doi = 10.1038/nature01580 | s2cid = 4347957 | bibcode = 2003Natur.423...33J }}{{cite journal | vauthors = Long SB, Campbell EB, Mackinnon R | title = Crystal structure of a mammalian voltage-dependent Shaker family K+ channel | journal = Science | volume = 309 | issue = 5736 | pages = 897–903 | date = August 2005 | pmid = 16002581 | doi = 10.1126/science.1116269 | s2cid = 6072007 | bibcode = 2005Sci...309..897L | doi-access = free }}

N-type inactivation is typically the faster inactivation mechanism, and is termed the "ball and chain" model.{{cite journal | vauthors = Antz C, Fakler B | title = Fast Inactivation of Voltage-Gated K(+) Channels: From Cartoon to Structure | journal = News in Physiological Sciences | volume = 13 | issue = 4 | pages = 177–182 | date = August 1998 | pmid = 11390785 | doi = 10.1152/physiologyonline.1998.13.4.177 | s2cid = 38134756 }} N-type inactivation involves interaction of the N-terminus of the channel, or an associated protein, which interacts with the pore domain and occludes the ion conduction pathway like a "ball". Alternatively, C-type inactivation is thought to occur within the selectivity filter itself, where structural changes within the filter render it non-conductive. There are a number of structural models of C-type inactivated K⁺ channel filters,{{cite journal | vauthors = Cheng WW, McCoy JG, Thompson AN, Nichols CG, Nimigean CM | title = Mechanism for selectivity-inactivation coupling in KcsA potassium channels | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 13 | pages = 5272–5277 | date = March 2011 | pmid = 21402935 | pmc = 3069191 | doi = 10.1073/pnas.1014186108 | doi-access = free | bibcode = 2011PNAS..108.5272C | author-link4 = Colin Nichols }}{{cite journal | vauthors = Cuello LG, Jogini V, Cortes DM, Perozo E | title = Structural mechanism of C-type inactivation in K(+) channels | journal = Nature | volume = 466 | issue = 7303 | pages = 203–208 | date = July 2010 | pmid = 20613835 | pmc = 3033749 | doi = 10.1038/nature09153 | bibcode = 2010Natur.466..203C }}{{cite journal | vauthors = Cuello LG, Jogini V, Cortes DM, Pan AC, Gagnon DG, Dalmas O, Cordero-Morales JF, Chakrapani S, Roux B, Perozo E | display-authors = 6 | title = Structural basis for the coupling between activation and inactivation gates in K(+) channels | journal = Nature | volume = 466 | issue = 7303 | pages = 272–275 | date = July 2010 | pmid = 20613845 | pmc = 3033755 | doi = 10.1038/nature09136 | bibcode = 2010Natur.466..272C }} although the precise mechanism remains unclear.

{{main|Potassium channel blocker}}

Potassium channel blockers inhibit the flow of potassium ions through the channel. They either compete with potassium binding within the selectivity filter or bind outside the filter to occlude ion conduction. An example of one of these competitors is quaternary ammonium ions, which bind at the extracellular face{{cite journal | vauthors = Luzhkov VB, Aqvist J | title = Ions and blockers in potassium channels: insights from free energy simulations | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1747 | issue = 1 | pages = 109–120 | date = February 2005 | pmid = 15680245 | doi = 10.1016/j.bbapap.2004.10.006 }}{{cite journal | vauthors = Luzhkov VB, Osterberg F, Aqvist J | title = Structure-activity relationship for extracellular block of K+ channels by tetraalkylammonium ions | journal = FEBS Letters | volume = 554 | issue = 1–2 | pages = 159–164 | date = November 2003 | pmid = 14596932 | doi = 10.1016/S0014-5793(03)01117-7 | s2cid = 32031835 | doi-access = free | bibcode = 2003FEBSL.554..159L }} or central cavity of the channel.{{cite journal | vauthors = Posson DJ, McCoy JG, Nimigean CM | title = The voltage-dependent gate in MthK potassium channels is located at the selectivity filter | journal = Nature Structural & Molecular Biology | volume = 20 | issue = 2 | pages = 159–166 | date = February 2013 | pmid = 23262489 | pmc = 3565016 | doi = 10.1038/nsmb.2473 }} For blocking from the central cavity quaternary ammonium ions are also known as open channel blockers, as binding classically requires the prior opening of the cytoplasmic gate.{{cite journal | vauthors = Choi KL, Mossman C, Aubé J, Yellen G | title = The internal quaternary ammonium receptor site of Shaker potassium channels | journal = Neuron | volume = 10 | issue = 3 | pages = 533–541 | date = March 1993 | pmid = 8461140 | doi = 10.1016/0896-6273(93)90340-w | s2cid = 33361945 }}

Barium ions can also block potassium channel currents,{{cite journal | vauthors = Piasta KN, Theobald DL, Miller C | title = Potassium-selective block of barium permeation through single KcsA channels | journal = The Journal of General Physiology | volume = 138 | issue = 4 | pages = 421–436 | date = October 2011 | pmid = 21911483 | pmc = 3182450 | doi = 10.1085/jgp.201110684 }}{{cite journal | vauthors = Neyton J, Miller C | title = Potassium blocks barium permeation through a calcium-activated potassium channel | journal = The Journal of General Physiology | volume = 92 | issue = 5 | pages = 549–567 | date = November 1988 | pmid = 3235973 | pmc = 2228918 | doi = 10.1085/jgp.92.5.549 }} by binding with high affinity within the selectivity filter.{{cite journal | vauthors = Lockless SW, Zhou M, MacKinnon R | title = Structural and thermodynamic properties of selective ion binding in a K+ channel | journal = PLOS Biology | volume = 5 | issue = 5 | pages = e121 | date = May 2007 | pmid = 17472437 | pmc = 1858713 | doi = 10.1371/journal.pbio.0050121 | doi-access = free }}{{cite journal | vauthors = Jiang Y, MacKinnon R | title = The barium site in a potassium channel by x-ray crystallography | journal = The Journal of General Physiology | volume = 115 | issue = 3 | pages = 269–272 | date = March 2000 | pmid = 10694255 | pmc = 2217209 | doi = 10.1085/jgp.115.3.269 }}{{cite journal | vauthors = Lam YL, Zeng W, Sauer DB, Jiang Y | title = The conserved potassium channel filter can have distinct ion binding profiles: structural analysis of rubidium, cesium, and barium binding in NaK2K | journal = The Journal of General Physiology | volume = 144 | issue = 2 | pages = 181–192 | date = August 2014 | pmid = 25024267 | pmc = 4113894 | doi = 10.1085/jgp.201411191 }}{{cite journal | vauthors = Guo R, Zeng W, Cui H, Chen L, Ye S | title = Ionic interactions of Ba2+ blockades in the MthK K+ channel | journal = The Journal of General Physiology | volume = 144 | issue = 2 | pages = 193–200 | date = August 2014 | pmid = 25024268 | pmc = 4113901 | doi = 10.1085/jgp.201411192 }} This tight binding is thought to underlie barium toxicity by inhibiting potassium channel activity in excitable cells.

Medically potassium channel blockers, such as 4-aminopyridine and 3,4-diaminopyridine, have been investigated for the treatment of conditions such as multiple sclerosis.{{cite journal | vauthors = Judge SI, Bever CT | title = Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment | journal = Pharmacology & Therapeutics | volume = 111 | issue = 1 | pages = 224–259 | date = July 2006 | pmid = 16472864 | doi = 10.1016/j.pharmthera.2005.10.006 }} Off target drug effects can lead to drug induced Long QT syndrome, a potentially life-threatening condition. This is most frequently due to action on the hERG potassium channel in the heart. Accordingly, all new drugs are preclinically tested for cardiac safety.

{{main|Potassium channel opener}}

{{expand section|date=May 2019}}

==Muscarinic potassium channel==

Image:Birth of an Idea.jpg. The sculpture was commissioned by Roderick MacKinnon based on the molecule's atomic coordinates that were determined by MacKinnon's group in 2001.]]

{{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 (I_KACh). These channels are a heterotetramer composed of two GIRK1 and two GIRK4 subunits.{{cite journal | vauthors = Krapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE | title = The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins | journal = Nature | volume = 374 | issue = 6518 | pages = 135–141 | date = March 1995 | pmid = 7877685 | doi = 10.1038/374135a0 | s2cid = 4334467 | bibcode = 1995Natur.374..135K }}{{cite journal | vauthors = Corey S, Krapivinsky G, Krapivinsky L, Clapham DE | title = Number and stoichiometry of subunits in the native atrial G-protein-gated K+ channel, IKACh | journal = The Journal of Biological Chemistry | volume = 273 | issue = 9 | pages = 5271–5278 | date = February 1998 | pmid = 9478984 | doi = 10.1074/jbc.273.9.5271 | doi-access = free }} Examples are potassium channels in the heart, which, when activated by parasympathetic signals through M2 muscarinic receptors, cause an outward current of potassium, which slows down the heart rate.{{cite journal | vauthors = Kunkel MT, Peralta EG | title = Identification of domains conferring G protein regulation on inward rectifier potassium channels | journal = Cell | volume = 83 | issue = 3 | pages = 443–449 | date = November 1995 | pmid = 8521474 | doi = 10.1016/0092-8674(95)90122-1 | s2cid = 14720432 | doi-access = free }}{{cite journal | vauthors = 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+ channel, IKACh | journal = Annals of the New York Academy of Sciences | volume = 868 | issue = 1 | pages = 386–398 | date = April 1999 | pmid = 10414308 | doi = 10.1111/j.1749-6632.1999.tb11300.x | url = http://www.annalsnyas.org/cgi/content/abstract/868/1/386 | url-status = dead | s2cid = 25949938 | bibcode = 1999NYASA.868..386W | archive-url = https://web.archive.org/web/20060129001228/http://www.annalsnyas.org/cgi/content/abstract/868/1/386 | archive-date = 2006-01-29 | url-access = subscription }}

Roderick MacKinnon commissioned Birth of an Idea, a {{convert|5|ft|adj=on}} tall sculpture based on the KcsA potassium channel.{{cite journal | vauthors = Ball P |date=March 2008 | title = The crucible: Art inspired by science should be more than just a pretty picture | journal = Chemistry World | volume = 5 | pages = 42–43 | url = http://www.rsc.org/chemistryworld/Issues/2008/March/ColumnThecrucible.asp | access-date=2009-01-12 | issue = 3 | name-list-style = vanc }} The artwork contains a wire object representing the channel's interior with a blown glass object representing the main cavity of the channel structure.

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• {{annotated link|Calcium channel}}
• {{annotated link|Inward-rectifier potassium ion channel}}
• {{annotated link|Potassium in biology}}
• {{annotated link|Potassium transporter family|Potassium transporter (Trk) family}}
• {{annotated link|Potassium uptake permease}}
• {{annotated link|Sodium ion channel}}

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{{Reflist|33em}}

• {{Proteopedia|Potassium channel}} in 3D
• {{MeshName|Potassium+Channels}}
• {{cite web | url = http://neuromuscular.wustl.edu/mother/chan.html#k | title = Potassium Channels | access-date = 2008-03-10 | author = Neuromuscular Disease Center | date = 2008-03-04 | publisher = Washington University in St. Louis }}

{{Ion channels|g3}}

{{channel blockers}}

Category:Ion channels

Category:Electrophysiology

Category:Integral membrane proteins