KCNE3: Difference between revisions

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'''Potassium voltage-gated channel, Isk-related family, member 3''' (KCNE3), also known as '''MinK-related peptide 2''' '''(MiRP2)'''  is a [[protein]] that in humans is encoded by the ''KCNE3'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: KCNE3 potassium voltage-gated channel, Isk-related family, member 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10008 }}</ref><ref name="pmid10219239">{{cite journal | vauthors = Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA | title = MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia | journal = Cell | volume = 97 | issue = 2 | pages = 175–87 | date = Apr 1999 | pmid = 10219239 | doi = 10.1016/S0092-8674(00)80728-X }}</ref>
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== Function ==
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[[Voltage-gated potassium channel]]s (K<sub>v</sub>) represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating [[neurotransmitter]] release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. KCNE3 encodes a member of the five-strong KCNE family of voltage-gated potassium (K<sub>v</sub>) channel ancillary or β subunits.
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KCNE3 is best known for modulating the KCNQ1 K<sub>v</sub> α subunit, but it also regulates hERG, K<sub>v</sub>2.1, K<sub>v</sub>3.x, K<sub>v</sub>4.x and K<sub>v</sub>12.2 in heterologous co-expression experiments and/or in vivo.
 
Co-assembly with KCNE3 converts KCNQ1 from a voltage-dependent delayed rectifier K+ channel to a constitutively open K+ channel with an almost linear current/voltage (I/V) relationship.<ref name=Schroeder>{{cite journal | vauthors = Schroeder BC, Waldegger S, Fehr S, Bleich M, Warth R, Greger R, Jentsch TJ | title = A constitutively open potassium channel formed by KCNQ1 and KCNE3 | journal = Nature | volume = 403 | issue = 6766 | pages = 196–9 | date = Jan 2000 | pmid = 10646604 | doi = 10.1038/35003200 }}</ref> KCNQ1-KCNE3 channels have been detected in the basolateral membrane of mouse small intestinal crypts, where they provide a driving force to regulate Cl- secretion.<ref name=Preston>{{cite journal | vauthors = Preston P, Wartosch L, Günzel D, Fromm M, Kongsuphol P, Ousingsawat J, Kunzelmann K, Barhanin J, Warth R, Jentsch TJ | title = Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in intestinal and tracheal Cl- transport | journal = The Journal of Biological Chemistry | volume = 285 | issue = 10 | pages = 7165–75 | date = Mar 2010 | pmid = 20051516 | doi = 10.1074/jbc.M109.047829 | pmc=2844166}}</ref> Specific amino acids within the transmembrane segment (V72) and extracellular domain (D54 and D55) of KCNE3 are important for its control of KCNQ1 voltage dependence.<ref name=Melman>{{cite journal | vauthors = Melman YF, Krumerman A, McDonald TV | title = A single transmembrane site in the KCNE-encoded proteins controls the specificity of KvLQT1 channel gating | journal = The Journal of Biological Chemistry | volume = 277 | issue = 28 | pages = 25187–94 | date = Jul 2002 | pmid = 11994278 | doi = 10.1074/jbc.M200564200 }}</ref><ref name=Choi>{{cite journal | vauthors = Choi E, Abbott GW | title = A shared mechanism for lipid- and beta-subunit-coordinated stabilization of the activated K+ channel voltage sensor | journal = FASEB Journal | volume = 24 | issue = 5 | pages = 1518–24 | date = May 2010 | pmid = 20040519 | doi = 10.1096/fj.09-145219 | pmc=2879946}}</ref> D54 and D55 interact electrostatically with R237 in the S4 segment of the KCNQ1 voltage sensor, helping to stabilize S4 in the activated state, which in turn locks open the channel unless the cell is held at a strongly hyperpolarizing (negative) membrane potential. The ability of KCNQ1-KCNE3 channels to remain open at weakly negative membrane potentials permits their activity in non-excitable, polarized epithelial cells such as those in the intestine.
 
KCNE3 also interacts with hERG, and when co-expressed in ''Xenopus laevis'' oocytes KCNE3 inhibits hERG activity by an unknown mechanism. It is not known whether hERG-KCNE3 complexes occur ''in vivo''.<ref name="Schroeder"/>
 
KCNE3 interacts with Kv2.1 ''in vitro'' and forms complexes with it in rat heart and brain. KCNE3 slows Kv2.1 activation and deactivation. KCNE3 can also regulate channels of the Kv3 subfamily, which are best known for permitting ultrarapid firing of neurons because of the extremely fast gating (activation and deactivation). KCNE3 moderately slows Kv3.1 and Kv3.2 activation and deactivation, and moderately speeds their C-type inactivation.<ref name="McCrossan brain">{{cite journal | vauthors = McCrossan ZA, Lewis A, Panaghie G, Jordan PN, Christini DJ, Lerner DJ, Abbott GW | title = MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain | journal = The Journal of Neuroscience | volume = 23 | issue = 22 | pages = 8077–91 | date = Sep 2003 | pmid = 12954870 }}</ref><ref name="McCrossan heart">{{cite journal | vauthors = McCrossan ZA, Roepke TK, Lewis A, Panaghie G, Abbott GW | title = Regulation of the Kv2.1 potassium channel by MinK and MiRP1 | journal = The Journal of Membrane Biology | volume = 228 | issue = 1 | pages = 1–14 | date = Mar 2009 | pmid = 19219384 | doi = 10.1007/s00232-009-9154-8 | pmc=2849987}}</ref>  It is possible that KCNE3 (and KCNE1 and 2) regulation of Kv3.1 and Kv3.2 helps to increase functional diversity within the Kv3 subfamily.<ref name=Lewis>{{cite journal | vauthors = Lewis A, McCrossan ZA, Abbott GW | title = MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating | journal = The Journal of Biological Chemistry | volume = 279 | issue = 9 | pages = 7884–92 | date = Feb 2004 | pmid = 14679187 | doi = 10.1074/jbc.M310501200 }}</ref> KCNE3 also regulates Kv3.4, augments its current by increasing the unitary conductance and by left-shifting the voltage dependence such that the channel can open at more negative voltages. This may allow Kv3.4-KCNE3 channels to contribute to setting resting membrane potential.<ref name="Abbott Cell 2">{{cite journal | vauthors = Abbott GW, Butler MH, Bendahhou S, Dalakas MC, Ptacek LJ, Goldstein SA | title = MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis | journal = Cell | volume = 104 | issue = 2 | pages = 217–31 | date = Jan 2001 | pmid = 11207363 | doi=10.1016/s0092-8674(01)00207-0}}</ref>
 
KCNE3 inhibits the fast inactivating K<sub>v</sub> channel K<sub>v</sub>4.3, which generates the transient outward Kv current (Ito) in human cardiac myocytes).<ref name="pmid16782062">{{cite journal | vauthors = Lundby A, Olesen SP | title = KCNE3 is an inhibitory subunit of the K<sub>v</sub>4.3 potassium channel | journal = Biochemical and Biophysical Research Communications | volume = 346 | issue = 3 | pages = 958–67 | date = Aug 2006 | pmid = 16782062 | doi = 10.1016/j.bbrc.2006.06.004 }}</ref>  similarly, KCNE3 was recently found to inhibit Kv4.2, and it is thought that this regulation modulates spike frequency and other electrical properties of auditory neurons.<ref name=Wang>{{cite journal | vauthors = Wang W, Kim HJ, Lee JH, Wong V, Sihn CR, Lv P, Perez Flores MC, Mousavi-Nik A, Doyle KJ, Xu Y, Yamoah EN | title = Functional significance of K+ channel β-subunit KCNE3 in auditory neurons | journal = The Journal of Biological Chemistry | volume = 289 | issue = 24 | pages = 16802–13 | date = Jun 2014 | pmid = 24727472 | doi = 10.1074/jbc.M113.545236 | pmc=4059123}}</ref>
 
Kv12.2 channels were found to be inhibited by endogenous KCNE3 (and KCNE1) subunits in ''Xenopus laevis'' oocytes. Thus, silencing of endogenous KCNE3 or KCNE1 using siRNA increases the macroscopic current of exogenously expressed Kv12.2. Kv12.2 forms a tripartite complex with KCNE1 and KCNE3 in oocytes, and may do so in mouse brain.<ref name=tripartite>{{cite journal | vauthors = Clancy SM, Chen B, Bertaso F, Mamet J, Jegla T | title = KCNE1 and KCNE3 beta-subunits regulate membrane surface expression of Kv12.2 K(+) channels in vitro and form a tripartite complex in vivo | journal = PLOS ONE | volume = 4 | issue = 7 | pages = e6330 | date = 22 July 2009 | pmid = 19623261 | doi = 10.1371/journal.pone.0006330 | pmc=2710002}}</ref> Previously, endogenous oocyte KCNE3 and KCNE1 were also found to inhibit exogenous hERG activity and slow the gating of exogenous Kv2.1.<ref>{{cite journal | vauthors = Anantharam A, Lewis A, Panaghie G, Gordon E, McCrossan ZA, Lerner DJ, Abbott GW | title = RNA interference reveals that endogenous Xenopus MinK-related peptides govern mammalian K+ channel function in oocyte expression studies | journal = The Journal of Biological Chemistry | volume = 278 | issue = 14 | pages = 11739–45 | date = Apr 2003 | pmid = 12529362 | doi = 10.1074/jbc.M212751200 }}</ref><ref>{{cite journal | vauthors = Gordon E, Roepke TK, Abbott GW | title = Endogenous KCNE subunits govern Kv2.1 K+ channel activation kinetics in Xenopus oocyte studies | journal = Biophysical Journal | volume = 90 | issue = 4 | pages = 1223–31 | date = Feb 2006 | pmid = 16326911 | doi = 10.1529/biophysj.105.072504 | pmc=1367273}}</ref>
 
== Structure ==
 
KCNE proteins are type I membrane proteins, and each assembles with one or more types of K<sub>v</sub> channel α subunit to modulate their gating kinetics and other functional parameters. KCNE3 has a larger predicted extracellular domain, and smaller predicted intracellular domain, in terms of primary structure, when compared to other KCNE proteins.<ref name="Abbott Cell 1">{{cite journal | vauthors = Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA | title = MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia | journal = Cell | volume = 97 | issue = 2 | pages = 175–87 | date = Apr 1999 | pmid = 10219239 | doi=10.1016/s0092-8674(00)80728-x}}</ref> As with other KCNE proteins, the transmembrane segment of KCNE3 is thought to be α-helical, and the extracellular domain also adopts a partly helical structure.<ref name="kcne3 structure">{{cite journal | vauthors = Kang C, Vanoye CG, Welch RC, Van Horn WD, Sanders CR | title = Functional delivery of a membrane protein into oocyte membranes using bicelles | journal = Biochemistry | volume = 49 | issue = 4 | pages = 653–5 | date = Feb 2010 | pmid = 20044833 | doi = 10.1021/bi902155t | pmc=2811756}}</ref>  KCNE3, like KCNE1 and possibly other KCNE proteins, are thought to make contact with the S4 of one α subunit and the S6 of another α subunit within the tetramer of Kv α subunits in a complex. No studies have as yet reported the number of KCNE3 subunits within a functional channel complex; it is likely to be either 2 or 4.
 
== Tissue distribution ==
 
KCNE3 is most prominently expressed in the colon, small intestine, and specific cell types in the stomach.<ref name=Grahammer>{{cite journal | vauthors = Grahammer F, Warth R, Barhanin J, Bleich M, Hug MJ | title = The small conductance K+ channel, KCNQ1: expression, function, and subunit composition in murine trachea | journal = The Journal of Biological Chemistry | volume = 276 | issue = 45 | pages = 42268–75 | date = Nov 2001 | pmid = 11527966 | doi = 10.1074/jbc.M105014200 }}</ref>  It is also detectable in the kidney and trachea, and depending on the species is also reportedly expressed at lower levels in the brain, heart and skeletal muscle. Specifically, KCNE3 was detected in rat, horse and human heart,<ref name="McCrossan heart"/><ref name=Finley>{{cite journal | vauthors = Finley MR, Li Y, Hua F, Lillich J, Mitchell KE, Ganta S, Gilmour RF, Freeman LC | title = Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 283 | issue = 1 | pages = H126–38 | date = Jul 2002 | pmid = 12063283 | doi = 10.1152/ajpheart.00622.2001 }}</ref><ref name="kcne3 brugada">{{cite journal | vauthors = Delpón E, Cordeiro JM, Núñez L, Thomsen PE, Guerchicoff A, Pollevick GD, Wu Y, Kanters JK, Larsen CT, Hofman-Bang J, Burashnikov E, Christiansen M, Antzelevitch C | title = Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome | journal = Circulation: Arrhythmia and Electrophysiology | volume = 1 | issue = 3 | pages = 209–18 | date = Aug 2008 | pmid = 19122847 | doi = 10.1161/CIRCEP.107.748103 | pmc=2585750}}</ref> but not in mouse heart.<ref name="Preston"/><ref name="Hu kcne3">{{cite journal | vauthors = Hu Z, Crump SM, Anand M, Kant R, Levi R, Abbott GW | title = Kcne3 deletion initiates extracardiac arrhythmogenesis in mice | journal = FASEB Journal | volume = 28 | issue = 2 | pages = 935–45 | date = Feb 2014 | pmid = 24225147 | doi = 10.1096/fj.13-241828 | pmc=3898654}}</ref> Some have observed KCNE3 expression in rat brain, rat and human skeletal muscle, and the mouse C2C12 skeletal muscle cell line, others have not detected it in these tissues in the mouse.<ref name="Preston"/><ref name="McCrossan brain"/><ref name="Abbott Cell 2"/><ref>{{cite journal | vauthors = Pannaccione A, Boscia F, Scorziello A, Adornetto A, Castaldo P, Sirabella R, Taglialatela M, Di Renzo GF, Annunziato L | title = Up-regulation and increased activity of KV3.4 channels and their accessory subunit MinK-related peptide 2 induced by amyloid peptide are involved in apoptotic neuronal death | journal = Molecular Pharmacology | volume = 72 | issue = 3 | pages = 665–73 | date = Sep 2007 | pmid = 17495071 | doi = 10.1124/mol.107.034868 }}</ref>
 
== Clinical significance ==
 
Genetic disruption of the Kcne3 gene in mice impairs intestinal cyclic AMP-stimulated chloride secretion via disruption of intestinal KCNQ1-KCNE3 channels that are important for regulating the chloride current.  KCNE3 also performs a similar function in mouse tracheal epithelium. Kcne3 deletion in mice also predisposes to ventricular arrhythmogenesis, but KCNE3 expression is not detectable in mouse heart. The mechanism for ventricular arrhythmogenesis was demonstrated to be indirect, and associated with autoimmune attack of the adrenal gland and secondary hyperaldosteronism (KCNE3 is not detectable in the adrenal gland).  The elevated serum aldosterone predisposes to arrhythmias triggered in a coronary artery ligation ischemia/reperfusion injury model.  Blockade of the aldosterone receptor with spironolactone removed the ventricular arrhythmia predisposition in ''Kcne3''-/- mice.  Kcne3 deletion also impairs auditory function because of the loss of regulation of Kv4.2 channels by KCNE3 in spiral ganglion neurons (SGNs) of the auditory system. KCNE3 is thought to regulate SGN firing properties and membrane potential via its modulation of Kv4.2.<ref name="Wang"/>
 
Mutations in human KCNE3 have been associated with [[hypokalemic periodic paralysis]]<ref name="entrez"/> and [[Brugada syndrome]].<ref name="pmid19122847">{{cite journal | vauthors = Delpón E, Cordeiro JM, Núñez L, Thomsen PE, Guerchicoff A, Pollevick GD, Wu Y, Kanters JK, Larsen CT, Hofman-Bang J, Burashnikov E, Christiansen M, Antzelevitch C | title = Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome | journal = Circulation: Arrhythmia and Electrophysiology | volume = 1 | issue = 3 | pages = 209–18 | date = Aug 2008 | pmid = 19122847 | pmc = 2585750 | doi = 10.1161/CIRCEP.107.748103 }}</ref>
 
The association with the R83H mutation in KCNE3 is controversial and other groups have detected the same mutation in individuals not exhibiting symptoms of periodic paralysis.<ref>{{cite journal | vauthors = Sternberg D, Tabti N, Fournier E, Hainque B, Fontaine B | title = Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis | journal = Neurology | volume = 61 | issue = 6 | pages = 857–9 | date = Sep 2003 | pmid = 14504341 | doi=10.1212/01.wnl.0000082392.66713.e3}}</ref> The mutation may instead be a benign polymorphism, or else it requires another genetic or environmental 'hit' before it becomes pathogenic.  Kv channels formed by Kv3.4 and R83H-KCNE3 have impaired function compared to wild-type channels, are less able to open at negative potentials and are sensitive to proton block during acidosis.<ref name="Abbott Cell 2"/><ref>{{cite journal | vauthors = Abbott GW, Butler MH, Goldstein SA | title = Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis | journal = FASEB Journal | volume = 20 | issue = 2 | pages = 293–301 | date = Feb 2006 | pmid = 16449802 | doi = 10.1096/fj.05-5070com }}</ref>


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KCNE3-linked Brugada syndrome is thought to arise because of mutant KCNE3 being unable to inhibit Kv4.3 channels in ventricular myocytes as it is suggested to do in healthy individuals. It appears that, unlike in mice, KCNE3 expression is detectable in human heart. It has not been reported whether people with KCNE3 mutations also have adrenal gland-related symptoms such as hyperaldosteronism.
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Potassium voltage-gated channel, Isk-related family, member 3
| HGNCid = 6243
| Symbol = KCNE3
| AltSymbols =; HOKPP; DKFZp781H21101; MGC102685; MGC129924; MiRP2
| OMIM = 604433
| ECnumber = 
| Homologene = 3994
| MGIid = 1891124
| GeneAtlas_image1 = PBB_GE_KCNE3_gnf1h00072_at_tn.png
| Function = {{GNF_GO|id=GO:0005249 |text = voltage-gated potassium channel activity}} {{GNF_GO|id=GO:0030955 |text = potassium ion binding}}
| Component = {{GNF_GO|id=GO:0008076 |text = voltage-gated potassium channel complex}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006811 |text = ion transport}} {{GNF_GO|id=GO:0006813 |text = potassium ion transport}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 10008
    | Hs_Ensembl = ENSG00000175538
    | Hs_RefseqProtein = NP_005463
    | Hs_RefseqmRNA = NM_005472
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 11
    | Hs_GenLoc_start = 73843536
    | Hs_GenLoc_end = 73856186
    | Hs_Uniprot = Q9Y6H6
    | Mm_EntrezGene = 57442
    | Mm_Ensembl = ENSMUSG00000035165
    | Mm_RefseqmRNA = XM_974792
    | Mm_RefseqProtein = XP_979886
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 100052780
    | Mm_GenLoc_end = 100058947
    | Mm_Uniprot = Q545H9
  }}
}}
'''Potassium voltage-gated channel, Isk-related family, member 3''', also known as '''KCNE3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: KCNE3 potassium voltage-gated channel, Isk-related family, member 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10008| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
KCNE3 mutations have been suggested to associate with Ménière’s disease in Japanese, a condition that presents as tinnitus, spontaneous vertigo, and periodic hearing loss,<ref>{{cite journal | vauthors = Doi K, Sato T, Kuramasu T, Hibino H, Kitahara T, Horii A, Matsushiro N, Fuse Y, Kubo T | title = Ménière's disease is associated with single nucleotide polymorphisms in the human potassium channel genes, KCNE1 and KCNE3 | journal = ORL; Journal for Oto-Rhino-Laryngology and Its Related Specialties | volume = 67 | issue = 5 | pages = 289–93 | date = 2005 | pmid = 16374062 | doi = 10.1159/000089410 }}</ref> however this association is also controversial and was not observed in a Caucasian population.<ref>{{cite journal | vauthors = Campbell CA, Della Santina CC, Meyer NC, Smith NB, Myrie OA, Stone EM, Fukushima K, Califano J, Carey JP, Hansen MR, Gantz BJ, Minor LB, Smith RJ | title = Polymorphisms in KCNE1 or KCNE3 are not associated with Ménière disease in the Caucasian population | journal = American Journal of Medical Genetics Part A | volume = 152A | issue = 1 | pages = 67–74 | date = Jan 2010 | pmid = 20034061 | doi = 10.1002/ajmg.a.33114 }}</ref>  In a study of tinnitus utilizing deep resequencing analysis, the authors were not able to prove or disprove association of KCNE3 sequence variation with tinnitus.<ref>{{cite journal | vauthors = Sand PG, Langguth B, Kleinjung T | title = Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in chronic tinnitus | journal = Behavioral and Brain Functions | volume = 7 | pages = 39 | date = 7 September 2011 | pmid = 21899751 | doi = 10.1186/1744-9081-7-39 | pmc=3180252}}</ref>
{{PBB_Summary
| section_title =  
| summary_text = Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the kidney. A missense mutation in this gene is associated with hypokalemic periodic paralysis.<ref name="entrez">{{cite web | title = Entrez Gene: KCNE3 potassium voltage-gated channel, Isk-related family, member 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10008| accessdate = }}</ref>
}}


==See also==
== See also ==
* [[Voltage-gated potassium channel]]
* [[Voltage-gated potassium channel]]
* [[KCNE1]]
* [[KCNE2]]
* [[KCNQ1]]


==References==
==Notes==
{{reflist|2}}
{{Academic-written review
| wikidate = 2015
| journal = [[Gene (journal)|Gene]]
| title  = {{#property:P1476|from=Q37028794}}
| authors = {{#property:P2093|from=Q37028794}}
| date    = {{#property:P577|from=Q37028794}}
| volume  = {{#property:P478|from=Q37028794}}
| issue  = {{#property:P433|from=Q37028794}}
| pages  = {{#property:P304|from=Q37028794}}
| doi    = {{#property:P356|from=Q37028794}}
| pmid    = {{#property:P698|from=Q37028794}}
| pmc    = {{#property:P932|from=Q37028794}}
}}


==Further reading==
== References ==
{{refbegin | 2}}
{{reflist|33em}}
{{PBB_Further_reading
 
| citations =
== Further reading ==
*{{cite journal | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791-806 |year= 1997 |pmid= 8889548 |doi= }}
{{refbegin|33em}}
*{{cite journal  | author=Abbott GW, Sesti F, Splawski I, ''et al.'' |title=MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. |journal=Cell |volume=97 |issue= 2 |pages= 175-87 |year= 1999 |pmid= 10219239 |doi=  }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
*{{cite journal  | author=Schroeder BC, Waldegger S, Fehr S, ''et al.'' |title=A constitutively open potassium channel formed by KCNQ1 and KCNE3. |journal=Nature |volume=403 |issue= 6766 |pages= 196-9 |year= 2000 |pmid= 10646604 |doi= 10.1038/35003200 }}
* {{cite journal | vauthors = Melman YF, Domènech A, de la Luna S, McDonald TV | title = Structural determinants of K<sub>v</sub>LQT1 control by the KCNE family of proteins | journal = The Journal of Biological Chemistry | volume = 276 | issue = 9 | pages = 6439–44 | date = Mar 2001 | pmid = 11104781 | doi = 10.1074/jbc.M010713200 }}
*{{cite journal | author=Melman YF, Domènech A, de la Luna S, McDonald TV |title=Structural determinants of KvLQT1 control by the KCNE family of proteins. |journal=J. Biol. Chem. |volume=276 |issue= 9 |pages= 6439-44 |year= 2001 |pmid= 11104781 |doi= 10.1074/jbc.M010713200 }}
* {{cite journal | vauthors = Dedek K, Waldegger S | title = Colocalization of KCNQ1/KCNE channel subunits in the mouse gastrointestinal tract | journal = Pflügers Archiv | volume = 442 | issue = 6 | pages = 896–902 | date = Sep 2001 | pmid = 11680623 | doi = 10.1007/s004240100609 }}
*{{cite journal | author=Abbott GW, Butler MH, Bendahhou S, ''et al.'' |title=MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. |journal=Cell |volume=104 |issue= 2 |pages= 217-31 |year= 2001 |pmid= 11207363 |doi=  }}
* {{cite journal | vauthors = Abbott GW, Goldstein SA | title = Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism | journal = FASEB Journal | volume = 16 | issue = 3 | pages = 390–400 | date = Mar 2002 | pmid = 11874988 | doi = 10.1096/fj.01-0520hyp }}
*{{cite journal  | author=Dedek K, Waldegger S |title=Colocalization of KCNQ1/KCNE channel subunits in the mouse gastrointestinal tract. |journal=Pflugers Arch. |volume=442 |issue= 6 |pages= 896-902 |year= 2002 |pmid= 11680623 |doi= }}
* {{cite journal | vauthors = Mazhari R, Nuss HB, Armoundas AA, Winslow RL, Marbán E | title = Ectopic expression of KCNE3 accelerates cardiac repolarization and abbreviates the QT interval | journal = The Journal of Clinical Investigation | volume = 109 | issue = 8 | pages = 1083–90 | date = Apr 2002 | pmid = 11956246 | pmc = 150950 | doi = 10.1172/JCI15062 }}
*{{cite journal | author=Abbott GW, Goldstein SA |title=Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism. |journal=FASEB J. |volume=16 |issue= 3 |pages= 390-400 |year= 2002 |pmid= 11874988 |doi= 10.1096/fj.01-0520hyp }}
* {{cite journal | vauthors = Dias Da Silva MR, Cerutti JM, Arnaldi LA, Maciel RM | title = A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 87 | issue = 11 | pages = 4881–4 | date = Nov 2002 | pmid = 12414843 | doi = 10.1210/jc.2002-020698 }}
*{{cite journal | author=Mazhari R, Nuss HB, Armoundas AA, ''et al.'' |title=Ectopic expression of KCNE3 accelerates cardiac repolarization and abbreviates the QT interval. |journal=J. Clin. Invest. |volume=109 |issue= 8 |pages= 1083-90 |year= 2002 |pmid= 11956246 |doi= }}
* {{cite journal | vauthors = Jurkat-Rott K, Lehmann-Horn F | title = Periodic paralysis mutation MiRP2-R83H in controls: Interpretations and general recommendation | journal = Neurology | volume = 62 | issue = 6 | pages = 1012–5 | date = Mar 2004 | pmid = 15037716 | doi = 10.1212/01.wnl.0000119392.29624.88 }}
*{{cite journal | author=Dias Da Silva MR, Cerutti JM, Arnaldi LA, Maciel RM |title=A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis. |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue= 11 |pages= 4881-4 |year= 2002 |pmid= 12414843 |doi=  }}
* {{cite journal | vauthors = Lundquist AL, Turner CL, Ballester LY, George AL | title = Expression and transcriptional control of human KCNE genes | journal = Genomics | volume = 87 | issue = 1 | pages = 119–28 | date = Jan 2006 | pmid = 16303284 | doi = 10.1016/j.ygeno.2005.09.004 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Panaghie G, Tai KK, Abbott GW | title = Interaction of KCNE subunits with the KCNQ1 K+ channel pore | journal = The Journal of Physiology | volume = 570 | issue = Pt 3 | pages = 455–67 | date = Feb 2006 | pmid = 16308347 | pmc = 1479883 | doi = 10.1113/jphysiol.2005.100644 }}
*{{cite journal | author=Jurkat-Rott K, Lehmann-Horn F |title=Periodic paralysis mutation MiRP2-R83H in controls: Interpretations and general recommendation. |journal=Neurology |volume=62 |issue= 6 |pages= 1012-5 |year= 2004 |pmid= 15037716 |doi= }}
* {{cite journal | vauthors = Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS | title = Transcriptome analysis of human gastric cancer | journal = Mammalian Genome | volume = 16 | issue = 12 | pages = 942–54 | date = Dec 2005 | pmid = 16341674 | doi = 10.1007/s00335-005-0075-2 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal | author=Lundquist AL, Turner CL, Ballester LY, George AL |title=Expression and transcriptional control of human KCNE genes. |journal=Genomics |volume=87 |issue= 1 |pages= 119-28 |year= 2006 |pmid= 16303284 |doi= 10.1016/j.ygeno.2005.09.004 }}
*{{cite journal | author=Panaghie G, Tai KK, Abbott GW |title=Interaction of KCNE subunits with the KCNQ1 K+ channel pore. |journal=J. Physiol. (Lond.) |volume=570 |issue= Pt 3 |pages= 455-67 |year= 2006 |pmid= 16308347 |doi= 10.1113/jphysiol.2005.100644 }}
*{{cite journal | author=Oh JH, Yang JO, Hahn Y, ''et al.'' |title=Transcriptome analysis of human gastric cancer. |journal=Mamm. Genome |volume=16 |issue= 12 |pages= 942-54 |year= 2006 |pmid= 16341674 |doi= 10.1007/s00335-005-0075-2 }}
*{{cite journal  | author=Doi K, Sato T, Kuramasu T, ''et al.'' |title=Ménière's disease is associated with single nucleotide polymorphisms in the human potassium channel genes, KCNE1 and KCNE3. |journal=ORL J. Otorhinolaryngol. Relat. Spec. |volume=67 |issue= 5 |pages= 289-93 |year= 2006 |pmid= 16374062 |doi= 10.1159/000089410 }}
*{{cite journal  | author=Abbott GW, Butler MH, Goldstein SA |title=Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis. |journal=FASEB J. |volume=20 |issue= 2 |pages= 293-301 |year= 2006 |pmid= 16449802 |doi= 10.1096/fj.05-5070com }}
*{{cite journal  | author=Lundby A, Olesen SP |title=KCNE3 is an inhibitory subunit of the Kv4.3 potassium channel. |journal=Biochem. Biophys. Res. Commun. |volume=346 |issue= 3 |pages= 958-67 |year= 2006 |pmid= 16782062 |doi= 10.1016/j.bbrc.2006.06.004 }}
*{{cite journal  | author=Pannaccione A, Boscia F, Scorziello A, ''et al.'' |title=Up-regulation and increased activity of KV3.4 channels and their accessory subunit MinK-related peptide 2 induced by amyloid peptide are involved in apoptotic neuronal death. |journal=Mol. Pharmacol. |volume=72 |issue= 3 |pages= 665-73 |year= 2007 |pmid= 17495071 |doi= 10.1124/mol.107.034868 }}
}}
{{refend}}
{{refend}}


== External links ==
== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK1517/  GeneReviews/NIH/NCBI/UW entry on Brugada syndrome]
* {{MeshName|KCNE3+protein,+human}}
* {{MeshName|KCNE3+protein,+human}}
* {{UCSC genome browser|KCNE3}}
* {{UCSC gene details|KCNE3}}


{{membrane-protein-stub}}
{{NLM content}}
{{NLM content}}
{{Ion channels}}
{{Ion channels|g3}}
{{WikiDoc Sources}}

Latest revision as of 00:26, 9 October 2017

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Potassium voltage-gated channel, Isk-related family, member 3 (KCNE3), also known as MinK-related peptide 2 (MiRP2) is a protein that in humans is encoded by the KCNE3 gene.[1][2]

Function

Voltage-gated potassium channels (Kv) represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. KCNE3 encodes a member of the five-strong KCNE family of voltage-gated potassium (Kv) channel ancillary or β subunits.

KCNE3 is best known for modulating the KCNQ1 Kv α subunit, but it also regulates hERG, Kv2.1, Kv3.x, Kv4.x and Kv12.2 in heterologous co-expression experiments and/or in vivo.

Co-assembly with KCNE3 converts KCNQ1 from a voltage-dependent delayed rectifier K+ channel to a constitutively open K+ channel with an almost linear current/voltage (I/V) relationship.[3] KCNQ1-KCNE3 channels have been detected in the basolateral membrane of mouse small intestinal crypts, where they provide a driving force to regulate Cl- secretion.[4] Specific amino acids within the transmembrane segment (V72) and extracellular domain (D54 and D55) of KCNE3 are important for its control of KCNQ1 voltage dependence.[5][6] D54 and D55 interact electrostatically with R237 in the S4 segment of the KCNQ1 voltage sensor, helping to stabilize S4 in the activated state, which in turn locks open the channel unless the cell is held at a strongly hyperpolarizing (negative) membrane potential. The ability of KCNQ1-KCNE3 channels to remain open at weakly negative membrane potentials permits their activity in non-excitable, polarized epithelial cells such as those in the intestine.

KCNE3 also interacts with hERG, and when co-expressed in Xenopus laevis oocytes KCNE3 inhibits hERG activity by an unknown mechanism. It is not known whether hERG-KCNE3 complexes occur in vivo.[3]

KCNE3 interacts with Kv2.1 in vitro and forms complexes with it in rat heart and brain. KCNE3 slows Kv2.1 activation and deactivation. KCNE3 can also regulate channels of the Kv3 subfamily, which are best known for permitting ultrarapid firing of neurons because of the extremely fast gating (activation and deactivation). KCNE3 moderately slows Kv3.1 and Kv3.2 activation and deactivation, and moderately speeds their C-type inactivation.[7][8] It is possible that KCNE3 (and KCNE1 and 2) regulation of Kv3.1 and Kv3.2 helps to increase functional diversity within the Kv3 subfamily.[9] KCNE3 also regulates Kv3.4, augments its current by increasing the unitary conductance and by left-shifting the voltage dependence such that the channel can open at more negative voltages. This may allow Kv3.4-KCNE3 channels to contribute to setting resting membrane potential.[10]

KCNE3 inhibits the fast inactivating Kv channel Kv4.3, which generates the transient outward Kv current (Ito) in human cardiac myocytes).[11] similarly, KCNE3 was recently found to inhibit Kv4.2, and it is thought that this regulation modulates spike frequency and other electrical properties of auditory neurons.[12]

Kv12.2 channels were found to be inhibited by endogenous KCNE3 (and KCNE1) subunits in Xenopus laevis oocytes. Thus, silencing of endogenous KCNE3 or KCNE1 using siRNA increases the macroscopic current of exogenously expressed Kv12.2. Kv12.2 forms a tripartite complex with KCNE1 and KCNE3 in oocytes, and may do so in mouse brain.[13] Previously, endogenous oocyte KCNE3 and KCNE1 were also found to inhibit exogenous hERG activity and slow the gating of exogenous Kv2.1.[14][15]

Structure

KCNE proteins are type I membrane proteins, and each assembles with one or more types of Kv channel α subunit to modulate their gating kinetics and other functional parameters. KCNE3 has a larger predicted extracellular domain, and smaller predicted intracellular domain, in terms of primary structure, when compared to other KCNE proteins.[16] As with other KCNE proteins, the transmembrane segment of KCNE3 is thought to be α-helical, and the extracellular domain also adopts a partly helical structure.[17] KCNE3, like KCNE1 and possibly other KCNE proteins, are thought to make contact with the S4 of one α subunit and the S6 of another α subunit within the tetramer of Kv α subunits in a complex. No studies have as yet reported the number of KCNE3 subunits within a functional channel complex; it is likely to be either 2 or 4.

Tissue distribution

KCNE3 is most prominently expressed in the colon, small intestine, and specific cell types in the stomach.[18] It is also detectable in the kidney and trachea, and depending on the species is also reportedly expressed at lower levels in the brain, heart and skeletal muscle. Specifically, KCNE3 was detected in rat, horse and human heart,[8][19][20] but not in mouse heart.[4][21] Some have observed KCNE3 expression in rat brain, rat and human skeletal muscle, and the mouse C2C12 skeletal muscle cell line, others have not detected it in these tissues in the mouse.[4][7][10][22]

Clinical significance

Genetic disruption of the Kcne3 gene in mice impairs intestinal cyclic AMP-stimulated chloride secretion via disruption of intestinal KCNQ1-KCNE3 channels that are important for regulating the chloride current. KCNE3 also performs a similar function in mouse tracheal epithelium. Kcne3 deletion in mice also predisposes to ventricular arrhythmogenesis, but KCNE3 expression is not detectable in mouse heart. The mechanism for ventricular arrhythmogenesis was demonstrated to be indirect, and associated with autoimmune attack of the adrenal gland and secondary hyperaldosteronism (KCNE3 is not detectable in the adrenal gland). The elevated serum aldosterone predisposes to arrhythmias triggered in a coronary artery ligation ischemia/reperfusion injury model. Blockade of the aldosterone receptor with spironolactone removed the ventricular arrhythmia predisposition in Kcne3-/- mice. Kcne3 deletion also impairs auditory function because of the loss of regulation of Kv4.2 channels by KCNE3 in spiral ganglion neurons (SGNs) of the auditory system. KCNE3 is thought to regulate SGN firing properties and membrane potential via its modulation of Kv4.2.[12]

Mutations in human KCNE3 have been associated with hypokalemic periodic paralysis[1] and Brugada syndrome.[23]

The association with the R83H mutation in KCNE3 is controversial and other groups have detected the same mutation in individuals not exhibiting symptoms of periodic paralysis.[24] The mutation may instead be a benign polymorphism, or else it requires another genetic or environmental 'hit' before it becomes pathogenic. Kv channels formed by Kv3.4 and R83H-KCNE3 have impaired function compared to wild-type channels, are less able to open at negative potentials and are sensitive to proton block during acidosis.[10][25]

KCNE3-linked Brugada syndrome is thought to arise because of mutant KCNE3 being unable to inhibit Kv4.3 channels in ventricular myocytes as it is suggested to do in healthy individuals. It appears that, unlike in mice, KCNE3 expression is detectable in human heart. It has not been reported whether people with KCNE3 mutations also have adrenal gland-related symptoms such as hyperaldosteronism.

KCNE3 mutations have been suggested to associate with Ménière’s disease in Japanese, a condition that presents as tinnitus, spontaneous vertigo, and periodic hearing loss,[26] however this association is also controversial and was not observed in a Caucasian population.[27] In a study of tinnitus utilizing deep resequencing analysis, the authors were not able to prove or disprove association of KCNE3 sequence variation with tinnitus.[28]

See also

Notes


References

  1. ↑ 1.0 1.1 "Entrez Gene: KCNE3 potassium voltage-gated channel, Isk-related family, member 3".
  2. ↑ Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA (Apr 1999). "MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia". Cell. 97 (2): 175–87. doi:10.1016/S0092-8674(00)80728-X. PMID 10219239.
  3. ↑ 3.0 3.1 Schroeder BC, Waldegger S, Fehr S, Bleich M, Warth R, Greger R, Jentsch TJ (Jan 2000). "A constitutively open potassium channel formed by KCNQ1 and KCNE3". Nature. 403 (6766): 196–9. doi:10.1038/35003200. PMID 10646604.
  4. ↑ 4.0 4.1 4.2 Preston P, Wartosch L, Günzel D, Fromm M, Kongsuphol P, Ousingsawat J, Kunzelmann K, Barhanin J, Warth R, Jentsch TJ (Mar 2010). "Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in intestinal and tracheal Cl- transport". The Journal of Biological Chemistry. 285 (10): 7165–75. doi:10.1074/jbc.M109.047829. PMC 2844166. PMID 20051516.
  5. ↑ Melman YF, Krumerman A, McDonald TV (Jul 2002). "A single transmembrane site in the KCNE-encoded proteins controls the specificity of KvLQT1 channel gating". The Journal of Biological Chemistry. 277 (28): 25187–94. doi:10.1074/jbc.M200564200. PMID 11994278.
  6. ↑ Choi E, Abbott GW (May 2010). "A shared mechanism for lipid- and beta-subunit-coordinated stabilization of the activated K+ channel voltage sensor". FASEB Journal. 24 (5): 1518–24. doi:10.1096/fj.09-145219. PMC 2879946. PMID 20040519.
  7. ↑ 7.0 7.1 McCrossan ZA, Lewis A, Panaghie G, Jordan PN, Christini DJ, Lerner DJ, Abbott GW (Sep 2003). "MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain". The Journal of Neuroscience. 23 (22): 8077–91. PMID 12954870.
  8. ↑ 8.0 8.1 McCrossan ZA, Roepke TK, Lewis A, Panaghie G, Abbott GW (Mar 2009). "Regulation of the Kv2.1 potassium channel by MinK and MiRP1". The Journal of Membrane Biology. 228 (1): 1–14. doi:10.1007/s00232-009-9154-8. PMC 2849987. PMID 19219384.
  9. ↑ Lewis A, McCrossan ZA, Abbott GW (Feb 2004). "MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating". The Journal of Biological Chemistry. 279 (9): 7884–92. doi:10.1074/jbc.M310501200. PMID 14679187.
  10. ↑ 10.0 10.1 10.2 Abbott GW, Butler MH, Bendahhou S, Dalakas MC, Ptacek LJ, Goldstein SA (Jan 2001). "MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis". Cell. 104 (2): 217–31. doi:10.1016/s0092-8674(01)00207-0. PMID 11207363.
  11. ↑ Lundby A, Olesen SP (Aug 2006). "KCNE3 is an inhibitory subunit of the Kv4.3 potassium channel". Biochemical and Biophysical Research Communications. 346 (3): 958–67. doi:10.1016/j.bbrc.2006.06.004. PMID 16782062.
  12. ↑ 12.0 12.1 Wang W, Kim HJ, Lee JH, Wong V, Sihn CR, Lv P, Perez Flores MC, Mousavi-Nik A, Doyle KJ, Xu Y, Yamoah EN (Jun 2014). "Functional significance of K+ channel β-subunit KCNE3 in auditory neurons". The Journal of Biological Chemistry. 289 (24): 16802–13. doi:10.1074/jbc.M113.545236. PMC 4059123. PMID 24727472.
  13. ↑ Clancy SM, Chen B, Bertaso F, Mamet J, Jegla T (22 July 2009). "KCNE1 and KCNE3 beta-subunits regulate membrane surface expression of Kv12.2 K(+) channels in vitro and form a tripartite complex in vivo". PLOS ONE. 4 (7): e6330. doi:10.1371/journal.pone.0006330. PMC 2710002. PMID 19623261.
  14. ↑ Anantharam A, Lewis A, Panaghie G, Gordon E, McCrossan ZA, Lerner DJ, Abbott GW (Apr 2003). "RNA interference reveals that endogenous Xenopus MinK-related peptides govern mammalian K+ channel function in oocyte expression studies". The Journal of Biological Chemistry. 278 (14): 11739–45. doi:10.1074/jbc.M212751200. PMID 12529362.
  15. ↑ Gordon E, Roepke TK, Abbott GW (Feb 2006). "Endogenous KCNE subunits govern Kv2.1 K+ channel activation kinetics in Xenopus oocyte studies". Biophysical Journal. 90 (4): 1223–31. doi:10.1529/biophysj.105.072504. PMC 1367273. PMID 16326911.
  16. ↑ Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA (Apr 1999). "MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia". Cell. 97 (2): 175–87. doi:10.1016/s0092-8674(00)80728-x. PMID 10219239.
  17. ↑ Kang C, Vanoye CG, Welch RC, Van Horn WD, Sanders CR (Feb 2010). "Functional delivery of a membrane protein into oocyte membranes using bicelles". Biochemistry. 49 (4): 653–5. doi:10.1021/bi902155t. PMC 2811756. PMID 20044833.
  18. ↑ Grahammer F, Warth R, Barhanin J, Bleich M, Hug MJ (Nov 2001). "The small conductance K+ channel, KCNQ1: expression, function, and subunit composition in murine trachea". The Journal of Biological Chemistry. 276 (45): 42268–75. doi:10.1074/jbc.M105014200. PMID 11527966.
  19. ↑ Finley MR, Li Y, Hua F, Lillich J, Mitchell KE, Ganta S, Gilmour RF, Freeman LC (Jul 2002). "Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart". American Journal of Physiology. Heart and Circulatory Physiology. 283 (1): H126–38. doi:10.1152/ajpheart.00622.2001. PMID 12063283.
  20. ↑ Delpón E, Cordeiro JM, Núñez L, Thomsen PE, Guerchicoff A, Pollevick GD, Wu Y, Kanters JK, Larsen CT, Hofman-Bang J, Burashnikov E, Christiansen M, Antzelevitch C (Aug 2008). "Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome". Circulation: Arrhythmia and Electrophysiology. 1 (3): 209–18. doi:10.1161/CIRCEP.107.748103. PMC 2585750. PMID 19122847.
  21. ↑ Hu Z, Crump SM, Anand M, Kant R, Levi R, Abbott GW (Feb 2014). "Kcne3 deletion initiates extracardiac arrhythmogenesis in mice". FASEB Journal. 28 (2): 935–45. doi:10.1096/fj.13-241828. PMC 3898654. PMID 24225147.
  22. ↑ Pannaccione A, Boscia F, Scorziello A, Adornetto A, Castaldo P, Sirabella R, Taglialatela M, Di Renzo GF, Annunziato L (Sep 2007). "Up-regulation and increased activity of KV3.4 channels and their accessory subunit MinK-related peptide 2 induced by amyloid peptide are involved in apoptotic neuronal death". Molecular Pharmacology. 72 (3): 665–73. doi:10.1124/mol.107.034868. PMID 17495071.
  23. ↑ Delpón E, Cordeiro JM, Núñez L, Thomsen PE, Guerchicoff A, Pollevick GD, Wu Y, Kanters JK, Larsen CT, Hofman-Bang J, Burashnikov E, Christiansen M, Antzelevitch C (Aug 2008). "Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome". Circulation: Arrhythmia and Electrophysiology. 1 (3): 209–18. doi:10.1161/CIRCEP.107.748103. PMC 2585750. PMID 19122847.
  24. ↑ Sternberg D, Tabti N, Fournier E, Hainque B, Fontaine B (Sep 2003). "Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis". Neurology. 61 (6): 857–9. doi:10.1212/01.wnl.0000082392.66713.e3. PMID 14504341.
  25. ↑ Abbott GW, Butler MH, Goldstein SA (Feb 2006). "Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis". FASEB Journal. 20 (2): 293–301. doi:10.1096/fj.05-5070com. PMID 16449802.
  26. ↑ Doi K, Sato T, Kuramasu T, Hibino H, Kitahara T, Horii A, Matsushiro N, Fuse Y, Kubo T (2005). "Ménière's disease is associated with single nucleotide polymorphisms in the human potassium channel genes, KCNE1 and KCNE3". ORL; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 67 (5): 289–93. doi:10.1159/000089410. PMID 16374062.
  27. ↑ Campbell CA, Della Santina CC, Meyer NC, Smith NB, Myrie OA, Stone EM, Fukushima K, Califano J, Carey JP, Hansen MR, Gantz BJ, Minor LB, Smith RJ (Jan 2010). "Polymorphisms in KCNE1 or KCNE3 are not associated with Ménière disease in the Caucasian population". American Journal of Medical Genetics Part A. 152A (1): 67–74. doi:10.1002/ajmg.a.33114. PMID 20034061.
  28. ↑ Sand PG, Langguth B, Kleinjung T (7 September 2011). "Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in chronic tinnitus". Behavioral and Brain Functions. 7: 39. doi:10.1186/1744-9081-7-39. PMC 3180252. PMID 21899751.

Further reading

External links

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