KCNE3

Last updated
KCNE3
Identifiers
Aliases KCNE3 , HOKPP, HYPP, MiRP2, potassium voltage-gated channel subfamily E regulatory subunit 3, BRGDA6
External IDs OMIM: 604433; MGI: 1891124; HomoloGene: 3994; GeneCards: KCNE3; OMA:KCNE3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005472

RefSeq (protein)

NP_005463

Location (UCSC) Chr 11: 74.45 – 74.47 Mb Chr 7: 99.83 – 99.83 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] [6]

Contents

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. [7] 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. [8] 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. [9] [10] 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. [7]

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. [11] [12] 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. [13] 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. [14]

KCNE3 inhibits the fast inactivating Kv channel Kv4.3, which generates the transient outward Kv current (Ito) in human cardiac myocytes. [15] 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. [16]

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. [17] Previously, endogenous oocyte KCNE3 and KCNE1 were also found to inhibit exogenous hERG activity and slow the gating of exogenous Kv2.1. [18] [19]

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. [20] 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. [21] 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. [22] 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, [12] [23] [24] but not in mouse heart. [8] [25] 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. [8] [11] [14] [26]

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. [16] While one group reported not observing skeletal muscle abnormalities in Kcne3 null mice, [27] a more comprehensive study showed clear skeletal muscle abnormalities as a result of germline Kcne3 deletion, including abnormal hindlimb clasping, altered contractile response to repetitive stimulation, and transcriptome remodeling. [28]

Mutations in human KCNE3 have been associated with hypokalemic periodic paralysis [14] and Brugada syndrome. [29]

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. [30] The mutation may instead be a benign polymorphism, or else it requires another genetic or environmental 'hit' before it becomes pathogenic, although the importance of KCNE3 in skeletal muscle function is supported by transgenic mouse studies. [28] 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. [31] [14]

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, [32] however this association is also controversial and was not observed in a Caucasian population. [33] 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. [34]

See also

Notes

Related Research Articles

<span class="mw-page-title-main">Repolarization</span> Change in membrane potential

In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential which has changed the membrane potential to a positive value. The repolarization phase usually returns the membrane potential back to the resting membrane potential. The efflux of potassium (K+) ions results in the falling phase of an action potential. The ions pass through the selectivity filter of the K+ channel pore.

<span class="mw-page-title-main">Romano–Ward syndrome</span> Medical condition

Romano–Ward syndrome is the most common form of congenital Long QT syndrome (LQTS), a genetic heart condition that affects the electrical properties of heart muscle cells. Those affected are at risk of abnormal heart rhythms which can lead to fainting, seizures, or sudden death. Romano–Ward syndrome can be distinguished clinically from other forms of inherited LQTS as it affects only the electrical properties of the heart, while other forms of LQTS can also affect other parts of the body.

<span class="mw-page-title-main">KvLQT1</span> Protein-coding gene in the species Homo sapiens

Kv7.1 (KvLQT1) is a potassium channel protein whose primary subunit in humans is encoded by the KCNQ1 gene. It's mutation causes Long QT syndrome, Kv7.1 is a voltage and lipid-gated potassium channel present in the cell membranes of cardiac tissue and in inner ear neurons among other tissues. In the cardiac cells, Kv7.1 mediates the IKs (or slow delayed rectifying K+) current that contributes to the repolarization of the cell, terminating the cardiac action potential and thereby the heart's contraction. It is a member of the KCNQ family of potassium channels.

<span class="mw-page-title-main">Voltage-gated potassium channel</span> Class of transport proteins

Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state.

<span class="mw-page-title-main">KCNE1</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily E member 1 is a protein that in humans is encoded by the KCNE1 gene.

<span class="mw-page-title-main">KCNE2</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily E member 2 (KCNE2), also known as MinK-related peptide 1 (MiRP1), is a protein that in humans is encoded by the KCNE2 gene on chromosome 21. MiRP1 is a voltage-gated potassium channel accessory subunit associated with Long QT syndrome. It is ubiquitously expressed in many tissues and cell types. Because of this and its ability to regulate multiple different ion channels, KCNE2 exerts considerable influence on a number of cell types and tissues. Human KCNE2 is a member of the five-strong family of human KCNE genes. KCNE proteins contain a single membrane-spanning region, extracellular N-terminal and intracellular C-terminal. KCNE proteins have been widely studied for their roles in the heart and in genetic predisposition to inherited cardiac arrhythmias. The KCNE2 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. More recently, roles for KCNE proteins in a variety of non-cardiac tissues have also been explored.

<span class="mw-page-title-main">KvLQT2</span> Protein-coding gene in humans

Kv7.2 (KvLQT2) is a voltage- and lipid-gated potassium channel protein coded for by the gene KCNQ2.

<span class="mw-page-title-main">Cation channel superfamily</span> Family of ion channel proteins

The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. These include the sodium, potassium, calcium, ryanodine receptor, HCN, CNG, CatSper, and TRP channels. This large group of ion channels apparently includes families 1.A.1, 1.A.2, 1.A.3, and 1.A.4 of the TCDB transporter classification.

<span class="mw-page-title-main">Potassium channel tetramerisation domain</span>

K+ channel tetramerisation domain is the N-terminal, cytoplasmic tetramerisation domain (T1) of voltage-gated K+ channels. It defines molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. It is distantly related to the BTB/POZ domain Pfam PF00651.

<span class="mw-page-title-main">KCNA4</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily A member 4 also known as Kv1.4 is a protein that in humans is encoded by the KCNA4 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

<span class="mw-page-title-main">KCNIP2</span> Protein-coding gene in the species Homo sapiens

Kv channel-interacting protein 2 also known as KChIP2 is a protein that in humans is encoded by the KCNIP2 gene.

<span class="mw-page-title-main">KCNB1</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel, Shab-related subfamily, member 1, also known as KCNB1 or Kv2.1, is a protein that, in humans, is encoded by the KCNB1 gene.

<span class="mw-page-title-main">KCND3</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily D member 3 also known as Kv4.3 is a protein that in humans is encoded by the KCND3 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

<span class="mw-page-title-main">KCNE4</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily E member 4, originally named MinK-related peptide 3 or MiRP3 when it was discovered, is a protein that in humans is encoded by the KCNE4 gene.

<span class="mw-page-title-main">KCNC4</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel, Shaw-related subfamily, member 4 (KCNC4), also known as Kv3.4, is a human gene.

<span class="mw-page-title-main">KCNS3</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily S member 3 (Kv9.3) is a protein that in humans is encoded by the KCNS3 gene. KCNS3 gene belongs to the S subfamily of the potassium channel family. It is highly expressed in pulmonary artery myocytes, placenta, and parvalbumin-containing GABA neurons in brain cortex. In humans, single-nucleotide polymorphisms of the KCNS3 gene are associated with airway hyperresponsiveness, whereas decreased KCNS3 mRNA expression is found in the prefrontal cortex of patients with schizophrenia.

<span class="mw-page-title-main">KCNC1</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily C member 1 is a protein that in humans is encoded by the KCNC1 gene.

<span class="mw-page-title-main">KCNG3</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily G member 3 is a protein that in humans is encoded by the KCNG3 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit.

<span class="mw-page-title-main">KCNE5</span> Protein-coding gene in the species Homo sapiens

KCNE1-like also known as KCNE1L is a protein that in humans is encoded by the KCNE1L gene.

<span class="mw-page-title-main">Guangxitoxin</span>

Guangxitoxin, also known as GxTX, is a peptide toxin found in the venom of the tarantula Plesiophrictus guangxiensis. It primarily inhibits outward voltage-gated Kv2.1 potassium channel currents, which are prominently expressed in pancreatic β-cells, thus increasing insulin secretion.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000175538 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000035165 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: KCNE3 potassium voltage-gated channel, Isk-related family, member 3".
  6. 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. S2CID   8507168.
  7. 1 2 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. Bibcode:2000Natur.403..196S. doi:10.1038/35003200. PMID   10646604. S2CID   205004809.
  8. 1 2 3 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.
  9. 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.
  10. 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.
  11. 1 2 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. doi:10.1523/JNEUROSCI.23-22-08077.2003. PMC   6740484 . PMID   12954870.
  12. 1 2 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.
  13. 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.
  14. 1 2 3 4 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. S2CID   16809594.
  15. 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.
  16. 1 2 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.
  17. 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. Bibcode:2009PLoSO...4.6330C. doi: 10.1371/journal.pone.0006330 . PMC   2710002 . PMID   19623261.
  18. 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.
  19. 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. Bibcode:2006BpJ....90.1223G. doi:10.1529/biophysj.105.072504. PMC   1367273 . PMID   16326911.
  20. 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. S2CID   8507168.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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. hdl: 11566/37512 . PMID   17495071. S2CID   7159171.
  27. Preston P, Wartosch L, Günzel D, Fromm M, Kongsuphol P, Ousingsawat J, Kunzelmann K, Barhanin J, Warth R, Jentsch TJ (March 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.
  28. 1 2 King EC, Patel V, Anand M, Zhao X, Crump SM, Hu Z, Weisleder N, Abbott GW (July 2017). "Targeted deletion of Kcne3 impairs skeletal muscle function in mice". FASEB Journal. 31 (7): 2937–2947. doi: 10.1096/fj.201600965RR . PMC   5472403 . PMID   28356343.
  29. 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.
  30. 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. S2CID   15449273.
  31. 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. S2CID   21538479.
  32. 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. S2CID   11258678.
  33. 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. S2CID   25363712.
  34. 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

This article incorporates text from the United States National Library of Medicine, which is in the public domain.