ouabain atp1a1 atp1a2 atp1a3 atp1a4 atp1b2 atp1b3 atp1b4 atp1b1 triphosphatase cofilin atp2b1 atp2b2 atp2b3 atp2b4 atp2c1 atp13a3 atp13a2 atp10a atp8b1 atp11b atp12a atp2a1 atp2a2 atp2a3 dystonia atp4a atp7b atp7a fphys
role of na/k pump in action potential
Na+ / k+ - ATPase - wikipedia Na / K - ATPase Jump to : navigation , search <Th_colspan="2"> Na+ / K+ ATPase pump <Td_colspan="2"> Sodium - potassium pump , E2 - Pi state . Calculated hydrocarbon boundaries of the lipid bilayer are shown as blue ( intracellular ) and red ( extracellular ) planes <Th_colspan="2"> Identifiers EC number 3.6. 3.9 <Th_colspan="2"> Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum <Td_colspan="2"> <Th_colspan="2"> ( show ) Search PMC articles PubMed articles NCBI proteins Flow of ions . Alpha and beta units . Na + / K + - ATPase ( sodium - potassium adenosine triphosphatase , also known as the Na + / K + pump or sodium -- potassium pump ) is an enzyme ( EC 3.6. 3.9 ) ( an electrogenic transmembrane ATPase ) found in the plasma membrane of all animal cells . The Na + / K + - ATPase enzyme is a solute pump that pumps sodium out of cells while pumping potassium into cells , both against their concentration gradients . This pumping is active ( i.e. it uses energy from ATP ) and is important for cell physiology . An example application is nerve conduction . It has antiporter - like activity , but since it moves both molecules against their concentration gradients it is not a true antiporter , which would require one solute to move with its gradient , not against it . Its simple function is to pump 3 sodium ions out for every 2 potassium ions taken in and since they both have equal ionic charges , this creates a electrochemical gradient between a cell and its exterior . The protein can also let the reverse operation happen , thus harnessing the energy it has stored in the form of an electric field potential . The reverse process is , unlike the forward , spontaneous . Contents ( hide ) 1 Sodium -- potassium pumps 2 Function 2.1 Resting potential 2.2 Transport 2.3 Controlling cell volume 2.4 Functioning as signal transducer 2.5 Controlling neuron activity states 3 Mechanism 4 Regulation 4.1 Endogenous 4.2 Exogenous 5 Discovery 6 Genes 7 Additional images 8 See also 9 References 10 External links Sodium -- potassium pumps ( edit ) The sodium pump is a membrane protein that uses energy in the form of adenosine triphosphate to perform active transport of sodium ions out of the cell in exchange for potassium ions into the cell . For every adenosine triphosphate molecule that the pump uses , three sodium ions are exported , while two potassium are imported ; there is hence a net export of a single positive charge per pump cycle . All mammals have four different sodium pump sub-types , or isoforms , that each has unique properties and tissue expression patterns . This was investigated by following the passage of radioactively labeled ions across the plasma membrane of certain cells . It was found that the concentrations of sodium and potassium ions on the two sides of the membrane are interdependent , suggesting that the same carrier transports both ions . It is now known that the carrier is an ATP - ase and that it pumps three sodium ions out of the cell for every two potassium ions pumped in . The sodium - potassium pump was discovered in the 1950s by a Danish scientist , Jens Christian Skou , who was awarded a Nobel Prize in 1997 . It marked an important step forward in the understanding of how ions get into and out of cells , and it has a particular significance for excitable cells such as nervous cells , which depend on this pump for responding to stimuli and transmitting impulses . Function ( edit ) The Na + / K + - ATPase helps maintain resting potential , effect transport , and regulate cellular volume . It also functions as a signal transducer / integrator to regulate MAPK pathway , ROS , as well as intracellular calcium . In most animal cells , the Na + / K + - ATPase is responsible for about 1 / 5 of the cell 's energy expenditure . For neurons , the Na + / K + - ATPase can be responsible for up to 2 / 3 of the cell 's energy expenditure . Resting potential ( edit ) The Na + / K + - ATPase , as well as effects of diffusion of the involved ions maintain the resting potential across the membranes . See also : Resting potential In order to maintain the cell membrane potential , cells keep a low concentration of sodium ions and high levels of potassium ions within the cell ( intracellular ) . The sodium - potassium pump mechanism moves 3 sodium ions out and moves 2 potassium ions in , thus , in total , removing one positive charge carrier from the intracellular space . ( Please see Mechanism for details ) . Transport ( edit ) Export of sodium from the cell provides the driving force for several secondary active transporters membrane transport proteins , which import glucose , amino acids , and other nutrients into the cell by use of the sodium gradient . Another important task of the Na + - K + pump is to provide a Na + gradient that is used by certain carrier processes . In the gut , for example , sodium is transported out of the reabsorbing cell on the blood ( interstitial fluid ) side via the Na + - K + pump , whereas , on the reabsorbing ( lumenal ) side , the Na + - glucose symporter uses the created Na + gradient as a source of energy to import both Na + and glucose , which is far more efficient than simple diffusion . Similar processes are located in the renal tubular system . Controlling cell volume ( edit ) Failure of the Na + - K + pumps can result in swelling of the cell . A cell 's osmolarity is the sum of the concentrations of the various ion species and many proteins and other organic compounds inside the cell . When this is higher than the osmolarity outside of the cell , water flows into the cell through osmosis . This can cause the cell to swell up and lyse . The Na + - K + pump helps to maintain the right concentrations of ions . Furthermore , when the cell begins to swell , this automatically activates the Na + - K + pump . Functioning as signal transducer ( edit ) Within the last decade ( when ? ) , many independent labs have demonstrated that , in addition to the classical ion transporting , this membrane protein can also relay extracellular ouabain - binding signalling into the cell through regulation of protein tyrosine phosphorylation . The downstream signals through ouabain - triggered protein phosphorylation events include activation of the mitogen - activated protein kinase ( MAPK ) signal cascades , mitochondrial reactive oxygen species ( ROS ) production , as well as activation of phospholipase C ( PLC ) and inositol triphosphate ( IP3 ) receptor ( IP3R ) in different intracellular compartments . Protein - protein interactions play a very important role in Na + - K + pump - mediated signal transduction . For example , Na + - K + pump interacts directly with Src , a non-receptor tyrosine kinase , to form a signaling receptor complex . Src kinase is inhibited by Na + - K + pump , while , upon ouabain binding , the Src kinase domain will be released and then activated . Based on this scenario , NaKtide , a peptide Src inhibitor derived from Na + - K + pump , was developed as a functional ouabain - Na + - K + pump - mediated signal transduction . Na + - K + pump also interacts with ankyrin , IP3R , PI3K , PLC - gamma and cofilin . Controlling neuron. activity states ( edit ) The Na + - K + pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons , accessory olfactory bulb mitral cells and probably other neuron types . This suggests that the pump might not simply be a homeostatic , `` housekeeping '' molecule for ionic gradients ; but could be a computation element in the cerebellum and the brain . Indeed , a mutation in the Na + - K + pump causes rapid onset dystonia parkinsonism , which has symptoms to indicate that it is a pathology of cerebellar computation . Furthermore , an ouabain block of Na + - K + pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia . Alcohol inhibits sodium - potassium pumps in the cerebellum and this is likely how it corrupts cerebellar computation and body co-ordination . The distribution of the Na + - K + pump on myelinated axons , in human brain , was demonstrated to be along the internodal axolemma , and not within the nodal axolemma as previously thought . Mechanism ( edit ) The sodium -- potassium exchange pump . The pump , after binding ATP , binds 3 intracellular Na + ions . ATP is hydrolyzed , leading to phosphorylation of the pump at a highly conserved aspartate residue and subsequent release of ADP . A conformational change in the pump exposes the Na + ions to the outside . The phosphorylated form of the pump has a low affinity for Na + ions , so they are released . The pump binds 2 extracellular K + ions . This causes the dephosphorylation of the pump , reverting it to its previous conformational state , transporting the K + ions into the cell . The unphosphorylated form of the pump has a higher affinity for Na + ions than K + ions , so the two bound K + ions are released . ATP binds , and the process starts again . Regulation ( edit ) Endogenous ( edit ) The Na + / K + - ATPase is upregulated by cAMP . Thus , substances causing an increase in cAMP upregulate the Na + / K + - ATPase . These include the ligands of the G - coupled GPCRs . In contrast , substances causing a decrease in cAMP downregulate the Na + / K + - ATPase . These include the ligands of the G - coupled GPCRs . Note : Early studies indicated the opposite effect , but these were later found to be inaccurate due to additional complicating factors . Exogenous ( edit ) The Na + - K + - ATPase can be pharmacologically modified by administrating drugs exogenously . For instance , Na + - K + - ATPase found in the membrane of heart cells is an important target of cardiac glycosides ( for example digoxin and ouabain ) , inotropic drugs used to improve heart performance by increasing its force of contraction . Muscle contraction is dependent on a 100 - to 10,000 - times - higher - than - resting intracellular Ca 2 + concentration , which is caused by Ca 2 + release from the muscle cells ' sarcoplasmic reticulum . Immediately after muscle contraction , intracellular Ca 2 + is quickly returned to its normal concentration by a carrier enzyme in the plasma membrane , and a calcium pump in sarcoplasmic reticulum , causing the muscle to relax . Since this carrier enzyme ( Na + - Ca 2 + translocator ) uses the Na gradient generated by the Na + - K + pump to remove Ca 2 + from the intracellular space , slowing down the Na + - K + pump results in a permanently elevated Ca 2 + level in the muscle , which may be the mechanism of the long - term inotropic effect of cardiac glycosides such as digoxin . Discovery ( edit ) Na + / K + - ATPase was discovered by Jens Christian Skou in 1957 while working as assistant professor at the Department of Physiology , University of Aarhus , Denmark . He published his work that year . In 1997 , he received one - half of the Nobel Prize in Chemistry `` for the first discovery of an ion - transporting enzyme , Na + , K + - ATPase . '' Genes ( edit ) Alpha : ATP1A1 ( 1 ) , ATP1A2 ( 2 ) , ATP1A3 ( 3 ) , ATP1A4 ( 4 ) . # 1 predominates in kidney . # 2 is also known as `` alpha ( + ) '' Beta : ATP1B1 ( 5 ) , ATP1B2 , ATP1B3 ( 6 ) , ATP1B4 Additional images ( edit ) Mechanism of the sodium - potassium exchange pump . See also ( edit ) Thyroid hormone V - ATPase References ( edit ) Jump up ^ Clausen MV , Hilbers F , Poulsen H ( June 2017 ) . `` The Structure and Function of the Na , K - ATPase Isoforms in Health and Disease . '' . Frontiers in Physiology. 8 . PMC 5459889 . PMID 28634454 . doi : 10.3389 / fphys. 2017.00371 . ^ Jump up to : Hall , John E. ; Guyton , Arthur C. ( 2006 ) . Textbook of medical physiology . St. Louis , Mo : Elsevier Saunders . ISBN 0 - 7216 - 0240 - 1 . Jump up ^ Howarth C , Gleeson P , Attwell D ( July 2012 ) . `` Updated energy budgets for neural computation in the neocortex and cerebellum '' . J. Cereb . Blood Flow Metab. 32 ( 7 ) : 1222 -- 32 . PMID 22434069 . doi : 10.1038 / jcbfm. 2012.35 . Jump up ^ Yuan Z , Cai T , Tian J , Ivanov AV , Giovannucci DR , Xie Z ( September 2005 ) . `` Na / K - ATPase tethers phospholipase C and IP3 receptor into a calcium - regulatory complex '' . Molecular Biology of the Cell. 16 ( 9 ) : 4034 -- 45 . PMC 1196317 . PMID 15975899 . doi : 10.1091 / mbc. E05 - 04 - 0295 . Jump up ^ Tian J , Cai T , Yuan Z , et al. ( January 2006 ) . `` Binding of Src to Na / K - ATPase forms a functional signaling complex '' . Molecular Biology of the Cell. 17 ( 1 ) : 317 -- 26 . PMC 1345669 . PMID 16267270 . doi : 10.1091 / mbc. E05 - 08 - 0735 . Jump up ^ Li Z , Cai T , Tian J , et al. ( July 2009 ) . `` NaKtide , a Na / K - ATPase - derived peptide Src inhibitor , antagonizes ouabain - activated signal transduction in cultured cells '' . The Journal of Biological Chemistry . 284 ( 31 ) : 21066 -- 76 . PMC 2742871 . PMID 19506077 . doi : 10.1074 / jbc. M109. 013821 . Jump up ^ Lee K , Jung J , Kim M , Guidotti G ( January 2001 ) . `` Interaction of the alpha subunit of Na , K - ATPase with cofilin '' . The Biochemical Journal . 353 ( 2 ) : 377 -- 85 . PMC 1221581 . PMID 11139403 . doi : 10.1042 / 0264 - 6021 : 3530377 . Jump up ^ Forrest MD , Wall MJ , Press DA , Feng J ( December 2012 ) . `` The Sodium - Potassium Pump Controls the Intrinsic Firing of the Cerebellar Purkinje Neuron '' . PLoS ONE . 7 ( 12 ) : e51169 . PMC 3527461 . PMID 23284664 . doi : 10.1371 / journal. pone. 0051169 . Jump up ^ Zylbertal , Asaph ; Kahan , Anat ; Ben - Shaul , Yoram ; Yarom , Yosef ; Wagner , Shlomo ( 2015 - 12 - 16 ) . `` Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells '' . PLOS Biology . 13 ( 12 ) : e1002319 . ISSN 1545 - 7885 . doi : 10.1371 / journal. pbio. 1002319 . Jump up ^ Zylbertal , Asaph ; Yarom , Yosef ; Wagner , Shlomo ( 2017 ) . `` The Slow Dynamics of Intracellular Sodium Concentration Increase the Time Window of Neuronal Integration : A Simulation Study '' . Frontiers in Computational Neuroscience. 11 . ISSN 1662 - 5188 . doi : 10.3389 / fncom. 2017.00085 . Jump up ^ Forrest MD ( December 2014 ) . `` The sodium - potassium pump is an information processing element in brain computation '' . Frontiers in Physiology. 5 ( 472 ) . doi : 10.3389 / fphys. 2014.00472 . Jump up ^ Cannon C ( July 2004 ) . `` Paying the Price at the Pump : Dystonia from Mutations in a Na / K - ATPase '' . Neuron. 43 ( 2 ) : 153 -- 154 . PMID 15260948 . doi : 10.1016 / j. neuron. 2004.07. 002 . Jump up ^ Calderon DP , Fremont R , Kraenzlin F , Khodakhah K ( March 2011 ) . `` The neural substrates of rapid - onset Dystonia - Parkinsonism '' . Nature Neuroscience. 14 ( 3 ) : 357 -- 65 . PMC 3430603 . PMID 21297628 . doi : 10.1038 / nn. 2753 . Jump up ^ Forrest MD ( April 2015 ) . `` Simulation of alcohol action upon a detailed Purkinje neuron model and a simpler surrogate model that runs > 400 times faster '' . BMC Neuroscience. 16 ( 27 ) . doi : 10.1186 / s12868 - 015 - 0162 - 6 . Jump up ^ Forrest , Michael ( April 2015 ) . `` the_neuroscience_reason_we_fall_over_when_drunk '' . Science 2.0 . Retrieved May 2015 . Check date values in : access - date = ( help ) Jump up ^ Young EA , Fowler CD , Kidd GJ , Chang A , Rudick R , Fisher E , Trapp BD ( April 2008 ) . `` Imaging correlates of decreased axonal Na / K ATPase in chronic multiple sclerosis lesions . '' . Ann Neurol. 63 ( 4 ) : 428 -- 35 . PMID 18438950 . doi : 10.1002 / ana. 21381 . Jump up ^ Burnier , Michel ( 2008 ) . Sodium In Health And Disease . CRC Press . p. 15 . ISBN 978 - 0 - 8493 - 3978 - 3 . Jump up ^ Skou JC ( February 1957 ) . `` The influence of some cations on an adenosine triphosphatase from peripheral nerves '' . Biochimica et Biophysica Acta. 23 ( 2 ) : 394 -- 401 . PMID 13412736 . doi : 10.1016 / 0006 - 3002 ( 57 ) 90343 - 8 . Jump up ^ Chemistry 1997 External links ( edit ) Sodium , Potassium ATPase at the US National Library of Medicine Medical Subject Headings ( MeSH ) RCSB Protein Data Bank : Sodium - Potassium Pump video Khan Academy . <Th_colspan="2"> ( show ) Membrane transport protein : ion pumps , ATPases / ATP synthase ( TC 3A2 - 3A3 ) F - , V - , and A-type ATPase ( 3. A. 2 ) H ( F - type ) H transporting , mitochondrial : ATP5A1 ATP5B ATP5C1 ATP5C2 ATP5D ATP5E ATP5F1 ATP5G1 ATP5G2 ATP5G3 ATP5H ATP5I ATP5J ATP5J2 ATP5L ATP5L2 ATP5O ATP5S H ( V - type ) H transporting , lysosomal : ATP6AP1 ATP6AP2 ATP6V1A ATP6V1B1 ATP6V1B2 ATP6V1C1 ATP6V1C2 ATP6V1D ATP6V1E1 ATP6V1E2 ATP6V1F ATP6V1G1 ATP6V1G2 ATP6V1G3 ATP6V1H ATP6V0A1 ATP6V0A2 ATP6V0A4 ATP6V0B ATP6V0C ATP6V0D1 ATP6V0D2 ATP6V0E ATP6V0E1 TCIRG1 A-ATPase found in Archea P - type ATPase ( 3. A. 3 ) 3. A. 3.1. 1 : Na / K transporting : ATP1A1 ATP1A2 ATP1A3 ATP1A4 ATP1B1 ATP1B2 ATP1B3 ATP1B4 ATP1G1 3. A. 3.1. 2 : H / K H / K exchanging : ATP4A ATP4B 3. A. 3.1. 4 : H / K transporting , nongastric : ATP12A 3. A. 3.2 : Ca ( SERCA , PMCA , SPCA ) / Ca transporting : ATP2A1 ATP2A2 ATP2A3 ATP2B1 ATP2B2 ATP2B3 ATP2B4 ATP2C1 3. A. 3.5 : Cu transporting : ATP7A ATP7B 3. A. 3.8. 8 : flippase : ATP8A2 Other / ungrouped : Na / K -- H Mg transporting : ATP3 Class I , type 8 : ATP8A1 ATP8B1 ATP8B2 ATP8B3 ATP8B4 Class II , type 9 : ATP9A ATP9B Class V , type 10 : ATP10A ATP10B ATP10D Class VI , type 11 : ATP11A ATP11B ATP11C type 13 : ATP13A1 ATP13A2 ATP13A3 ATP13A4 ATP13A5 <Td_colspan="2"> see also ATPase disorders <Th_colspan="2"> ( show ) Hydrolases : acid anhydride hydrolases ( EC 3.6 ) 3.6. 1 Pyrophosphatase Inorganic Thiamine Apyrase Thiamine - triphosphatase 3.6. 2 Adenylylsulfatase Phosphoadenylylsulfatase 3.6. 3 - 4 : ATPase 3.6. 3 Cu++ ( 3.6. 3.4 ) Menkes / ATP7A Wilson / ATP7B Ca+ ( 3.6. 3.8 ) SERCA ATP2A1 ATP2A2 ATP2A3 Plasma membrane ATP2B1 ATP2B2 ATP2B3 ATP2B4 SPCA ATP2C1 ATP2C2 Na+ / K+ ( 3.6. 3.9 ) ATP1A1 ATP1A2 ATP1A3 ATP1A4 ATP1B1 ATP1B2 ATP1B3 ATP1B4 H+ / K+ ( 3.6. 3.10 ) ATP4A Other P - type ATPase ATP8B1 ATP10A ATP11B ATP12A ATP13A2 ATP13A3 3.6. 4 Dynein Kinesin Myosin Katanin 3.6. 5 : GTPase 3.6. 5.1 : Heterotrimeric G protein G G GNAI1 GNAI2 GNAI3 G GNAQ GNA11 G GNA12 GNA13 Transducin GNAT1 GNAT2 Gustducin GNAT3 3.6. 5.2 : Small GTPase > Ras superfamily Rho family of GTPases : Cdc42 CDC42 TC10 TCL RhoUV RhoU RhoV Rac Rac1 2 3 RhoG RhoBTB 1 2 RhoH Rho A B C Rnd 1 2 3 RhoDF RhoF RhoD other : Ras HRAS KRAS NRAS Rab RAB23 RAB27 Arf ARF6 SAR1B ARL13B ARL6 Ran Rheb Rap RGK 3.6. 5.3 : Protein - synthesizing GTPase Prokaryotic IF - 2 EF - Tu EF - G Eukaryotic 3.6. 5.5 - 6 : Polymerization motors Dynamin Tubulin <Th_colspan="2"> ( show ) Enzymes Activity Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Regulation Allosteric regulation Cooperativity Enzyme inhibitor Classification EC number Enzyme superfamily Enzyme family List of enzymes Kinetics Enzyme kinetics Eadie -- Hofstee diagram Hanes -- Woolf plot Lineweaver -- Burk plot Michaelis -- Menten kinetics Types EC1 Oxidoreductases ( list ) EC2 Transferases ( list ) EC3 Hydrolases ( list ) EC4 Lyases ( list ) EC5 Isomerases ( list ) EC6 Ligases ( list ) Molecular and Cellular Biology portal Retrieved from `` https://en.wikipedia.org/w/index.php?title=Na%2B/K%2B-ATPase&oldid=802361951 '' Categories : EC 3.6. 3 Transport proteins Hidden categories : CS1 errors : dates All articles with unsourced statements Articles with unsourced statements from January 2013 Articles with unsourced statements from February 2010 Talk Article Talk More Search Contents About Wikipedia In other projects Wikimedia Commons العربية Български Bosanski Català Čeština Dansk Deutsch Eesti Ελληνικά Español فارسی Français Galego 한국어 Bahasa Indonesia Italiano עברית Lietuvių Magyar Nederlands 日本 語 Polski Português Русский Simple English Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska Українська 中文 Edit links This page was last edited on 25 September 2017 , at 18 : 02 . 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