Kv11.1

Target id: 572

Nomenclature: Kv11.1

Family: Voltage-gated potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Kv11.1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1159 7q35-q36 KCNH2 potassium voltage-gated channel subfamily H member 2
Mouse 6 1 1162 5 A3 Kcnh2 potassium voltage-gated channel, subfamily H (eag-related), member 2
Rat 6 1 1163 4q11 Kcnh2 potassium voltage-gated channel subfamily H member 2
Previous and Unofficial Names
eag-related protein 1 | erg1 | ERG-1 | ether-a-go-go-related gene potassium channel 1 | ether-à-go-go-related gene | HERG | potassium channel, voltage gated eag related subfamily H, member 2 | potassium voltage-gated channel, subfamily H (eag-related), member 2
Database Links
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kv11.3 73
Kv11.2 73
Auxiliary Subunits
Name References
KCNE1, minK 17,42,74
KCNE2, miRP1 1,25
Other Associated Proteins
Name References
GM130 54
KCR1 38,45
FKBP38 69
Hjd-2 69
Hop 69
Bag-2 69
Hsc 70 16
Hsp90 16
caveolin-3 27
Associated Protein Comments
Controversy regarding MiRP1 interaction [72]
Functional Characteristics
cardiac IKR
Ion Selectivity and Conductance
Species:  Human
Macroscopic current rectification:  IKr
References:  30,58-60,63,68
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - - HEK 293 cells. Human
Inactivation  -90.0 - 63
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -35.0 – -15.0 100.0 58,60,68 Xenopus laevis oocyte Human
Inactivation  - 4.0 – 20.0 30,59
Comments  τ activation at 20mV, τ inactivation at 40mV

Under voltage clamp, longer pulses drive V0.5 to more negative potentials. Removing the amino terminus causes negative shift that is no longer sensitive to pulse duration [60,68].

C-type inactivation mediates the strong rectifying properties characteristic of Kv11.1 / hERG channels [59,63].

The amino terminus slows deactivation and promotes C-type inactivation [71]. See [70] for detailed kinetic analysis of all hERG gating transitions, and see [57] for summary.

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
A-935142 Hs - - - 2x10-5 - 64
Conc range: 2x10-5 M [64]
PD-118057 Hs - - - 1x10-5 - 77
Conc range: 1x10-5 M [77]
RPR260243 Hs - - - 3x10-6 - 34
Conc range: 3x10-6 M [34]
PD-307243 Hs - - - 2x10-6 - 24
Conc range: 2x10-6 M [24]
rottlerin Hs Activation 6.5 pEC50 - - 75
pEC50 6.5 [75]
ginsenoside Rg3 Hs Activation 6.4 pEC50 - - 9
pEC50 6.4 [9]
ICA-105574 Hs Activation 6.3 pEC50 - - 20
pEC50 6.3 [20]
NS1643 Hs Activation 5.0 pEC50 - - 8,28
pEC50 5.0 [8,28]
VU0405601 Hs Activation 4.9 – 5.0 pEC50 - - 48
pEC50 4.9 – 5.0 [48]
KB-130015 Hs Activation 4.9 pEC50 - - 21
pEC50 4.9 [21]
NS3623 Hs Activation 4.1 pEC50 - - 29
pEC50 4.1 [29]
Activator Comments
NS1643: Slows inactivation and thus gives appearance of activating, does not directly affect activation [8,28]
Mallotoxin: speeds activation and slows deactivation [75].
RPR260243 is an activator of Kv11.1, and has been demonstrated to inhibit channel closure, which leads to a persistent HERG channel current upon repolarisation [34].

For a review of hERG activators see [56].
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
nemiralisib Hs Inhibition 5.5 pIC50 - - 13
pIC50 5.5 (IC50 3.162x10-6 M) [13]
Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
APETx-1 Hs - 7.4 pKd - - 76
pKd 7.4 [76]
APETx-1 Hs Inhibition 7.5 pIC50 - - 12
pIC50 7.5 [12]
Gating Inhibitor Comments
APETx-1 is a sea anemone toxin which inhibits by binding to the S3b region of the voltage sensor [76].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
ErgTx-1 Hs - 8.3 pKd - -70.0 51
pKd 8.3 [51]
Holding voltage: -70.0 mV
BeKm-1 Hs - 8.2 pKd - - 37
pKd 8.2 [37]
ErgTx-1 Rn - 8.2 pKd - -70.0 51
pKd 8.2 [51]
Holding voltage: -70.0 mV
γ-KTx1.7 Hs - 7.9 pKd - - 52
pKd 7.9 [52]
BeKm-1 Rn - 7.7 pKd - -70.0 51
pKd 7.7 [51]
Holding voltage: -70.0 mV
E4031 Rn - 7.0 pKd - - 61
pKd 7.0 [61]
dofetilide Hs Inhibition 8.2 pKi - - 62
pKi 8.2 (Ki 6.4x10-9 M) [62]
astemizole Hs - 9.0 pIC50 - - 79
pIC50 9.0 (IC50 1x10-9 M) [79]
E4031 Hs - 8.1 pIC50 - - 78
pIC50 8.1 (IC50 7.7x10-9 M) [78]
ibutilide Hs - 7.6 – 8.0 pIC50 - - 35,47
pIC50 7.6 – 8.0 (IC50 2.51x10-8 – 1x10-8 M) [35,47]
cisapride Hs - 7.4 pIC50 - - 50
pIC50 7.4 (IC50 4.45x10-8 M) [50]
terfenadine Hs - 7.3 pIC50 - - 50
pIC50 7.3 (IC50 5.6x10-8 M) [50]
AZD3778 Hs Inhibition 4.8 pIC50 - - 6
pIC50 4.8 (IC50 1.58x10-5 M) [6]
disopyramide Hs Inhibition 4.0 pIC50 - - 35
pIC50 4.0 (IC50 9.12x10-5 M) [35]
View species-specific channel blocker tables
Channel Blocker Comments
E-4031, dofetilide, terfenadine, and many other compounds, see [66] for review.
Drugs cross the cell membrane and enter hERG channels through open intracellular gate, where they may become trapped when channels close. Binding sites involve F656 and Y652 in the channel vestibule [40,43-44]. There remains controversy as to whether inhibition arises from a simple pore block mechanism or more complex processes also involving inactivation.
See [15,22] for studies involving Kv10 / EAG that provide intriguing insights into the role of inactivation in Kv11.1 / hERG drug binding.

BeKm-1 is also a scorpion toxin which binds to the outer mouth of the pore [37]. ERG Toxin-1 / CnERG1 is a low nM binding scorpion toxin which inhibits by binding to outer mouth of the pore [31,46].

Compounds have been identified that increase Kv11.1 function by enhancing ER export and may be useful as therapeutic agents in treating inherited or acquired LQTS [49].
Tissue Distribution
CNS - widely expressed, developing spinal cord
Species:  Rat
Technique:  In situ hybridisation
References:  18,26,55,61
Tissue Distribution Comments
Detected in the heart of all mammalian species studied to date, using electrophysiology, biochemistry and Northern blot. Also cancer cells of many types [4], and gut, pancreatic beta cells and many others.
Physiological Functions
hERG in smooth muscle contractility
Species:  Human
Tissue:  Jejenum
References:  14
Role in pancreatic beta cell secretion
Species:  Human
Tissue:  Pancreatic islet cells
References:  53
hERG channels regulate excitability in developing neurons
Species:  Mouse
Tissue:  Neural crest, spinal cord neurons
References:  5,18-19
In the human heart, Kv11.1 / hERG 1a and 1b subunits mediate the repolarizing cardiac current IKr. IKr peaks during late repolarization as a result of rebound from inactivation and slow deactivation. Loss of hERG function by mutations of the hERG gene (KCNH2) or by block by drugs intended largely for other therapeutic targets causes long QT syndrome (LQTS), which can lead to catastrophic arrhythmias and sudden death.
Species:  Human
Tissue:  Heart
References:  58,67,78
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0002128 abnormal blood circulation PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0001544 abnormal cardiovascular system physiology PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0000428 abnormal craniofacial morphology PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0000267 abnormal heart development PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0000266 abnormal heart morphology PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0000269 abnormal looping morphogenesis PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0004145 abnormal muscle electrophysiology PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0006126 abnormal outflow tract development PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0001698 decreased embryo size PMID: 18948620 
Kcnh2tm1Hjd Kcnh2tm1Hjd/Kcnh2tm1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0005333 decreased heart rate PMID: 12612061 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0006207 embryonic lethality during organogenesis PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0001636 irregular heartbeat PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0005312 pericardial effusion PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341722  MP:0006341 small first branchial arch PMID: 18948620 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Long QT syndrome 2; LQT2
Synonyms: Long QT syndrome [Disease Ontology: DOID:2843]
Romano-Ward syndrome [Orphanet: ORPHA101016]
Disease Ontology: DOID:2843
OMIM: 613688
Orphanet: ORPHA101016
Role: 
Therapeutic use:  hERG stable cell lines are used for counterscreening drugs in development as a safety test to prevent acquired LQTS
References:  2,11,23,58,66-67
Disease:  Schizophrenia
Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140
Role: 
References:  3,32
Disease:  Short QT syndrome-1; SQT1
Synonyms: Familial short QT syndrome [Orphanet: ORPHA51083]
OMIM: 609620
Orphanet: ORPHA51083
References:  7,65
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human N588K 1764C>G/A Two different point mutations at nucleotide 1764, a C->G transversion, and a C->A transversion, both cause an amino acid change from asparagine to lysine at position 588. 7
Missense Human T618I 1853C>T 65
Clinically-Relevant Mutations and Pathophysiology Comments
There are more than 200 mutations known for the KCNH2 gene.
Gene Expression and Pathophysiology
hERG subunits are aberrantly expressed (either over or mis-expressed) in many tumour types
Tissue or cell type:  Human primary cancers, tumour cell lines
Pathophysiology:  Putatively; Control of cell proliferation, regulation of tumour cell invasiveness (involving integrin family), control of tumour cell neoangiogensis (involving angiogenic factors).
Species:  Human
Technique:  -
References:  4
Application of NS1643 (hERG agonist) inhibits proliferation of breast cancer cells by activating a senescence program
Tissue or cell type:  Breast cancer cells
Pathophysiology:  Decreased proliferation is accompanied by arrest of the cell cycle in G0/G1 phase
Species:  None
Technique: 
References:  39
CpG methylation of KCNH2 is inversely correlated with tumour gene expression in clear-cell ovarian tumours
Tissue or cell type:  Clear-cell ovarian tumours
Pathophysiology: 
Species:  Human
Technique: 
References:  10
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  hERG USO
Amino acids:  888
Nucleotide accession: 
Protein accession: 
References:  38
Type:  Splice variant
Species:  Human
Description:  hERG 1b variant; also referred to as isoform c. These subunits reduce rectification by increasing the rate of recovery from inactivation, thus yielding larger amplitude currents during ventricular action potential. Leads to somewhat reduced E-4031 sensitivity.
Amino acids:  819
Nucleotide accession: 
Protein accession: 
References:  33,36,40-41
Type:  Splice variant
Species:  Human
Description:  Isoform a
Amino acids:  1159
Nucleotide accession: 
Protein accession: 
Type:  Splice variant
Species:  Human
Description:  KCNH2-3.1
Amino acids:  1063
References:  32
Biologically Significant Variant Comments
These are alternative transcripts rather than splice variants.

References

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1. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA. (1999) MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell97 (2): 175-87. [PMID:10219239]

2. Anderson CL, Delisle BP, Anson BD, Kilby JA, Will ML, Tester DJ, Gong Q, Zhou Z, Ackerman MJ, January CT. (2006) Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation113 (3): 365-73. [PMID:16432067]

3. Apud JA, Zhang F, Decot H, Bigos KL, Weinberger DR. (2012) Genetic variation in KCNH2 associated with expression in the brain of a unique hERG isoform modulates treatment response in patients with schizophrenia. Am J Psychiatry169 (7): 725-34. [PMID:22706279]

4. Arcangeli A. (2005) Expression and role of hERG channels in cancer cells. Novartis Found. Symp.266: 225-32; discussion 232-4. [PMID:16050271]

5. Arcangeli A, Rosati B, Cherubini A, Crociani O, Fontana L, Ziller C, Wanke E, Olivotto M. (1997) HERG- and IRK-like inward rectifier currents are sequentially expressed during neuronal development of neural crest cells and their derivatives. Eur. J. Neurosci.9 (12): 2596-604. [PMID:9517465]

6. Bahl A, Barton P, Bowers K, Brough S, Evans R, Luckhurst CA, Mochel T, Perry MW, Rigby A, Riley RJ et al.. (2012) The discovery of CCR3/H1 dual antagonists with reduced hERG risk. Bioorg. Med. Chem. Lett.22 (21): 6688-93. [PMID:23031591]

7. Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M, Menendez TM, Brugada J, Pollevick GD, Wolpert C et al.. (2004) Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation109 (1): 30-5. [PMID:14676148]

8. Casis O, Olesen SP, Sanguinetti MC. (2006) Mechanism of action of a novel human ether-a-go-go-related gene channel activator. Mol. Pharmacol.69 (2): 658-65. [PMID:16284303]

9. Choi SH, Shin TJ, Hwang SH, Lee BH, Kang J, Kim HJ, Jo SH, Choe H, Nah SY. (2011) Ginsenoside Rg(3) decelerates hERG K(+) channel deactivation through Ser631 residue interaction. Eur. J. Pharmacol.663 (1-3): 59-67. [PMID:21586280]

10. Cicek MS, Koestler DC, Fridley BL, Kalli KR, Armasu SM, Larson MC, Wang C, Winham SJ, Vierkant RA, Rider DN et al.. (2013) Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel. Hum. Mol. Genet.22 (15): 3038-47. [PMID:23571109]

11. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell80 (5): 795-803. [PMID:7889573]

12. Diochot S, Loret E, Bruhn T, Béress L, Lazdunski M. (2003) APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks voltage-gated human ether-a-go-go-related gene potassium channels. Mol. Pharmacol.64 (1): 59-69. [PMID:12815161]

13. Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL et al.. (2015) Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J. Med. Chem.58 (18): 7381-99. [PMID:26301626]

14. Farrelly AM, Ro S, Callaghan BP, Khoyi MA, Fleming N, Horowitz B, Sanders KM, Keef KD. (2003) Expression and function of KCNH2 (HERG) in the human jejunum. Am. J. Physiol. Gastrointest. Liver Physiol.284 (6): G883-95. [PMID:12736144]

15. Ficker E, Dennis AT, Wang L, Brown AM. (2003) Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG. Circ. Res.92 (12): e87-100. [PMID:12775586]

16. Ficker E, Jarolimek W, Kiehn J, Baumann A, Brown AM. (1998) Molecular determinants of dofetilide block of HERG K+ channels. Circ. Res.82 (3): 386-95. [PMID:9486667]

17. Finley MR, Li Y, Hua F, Lillich J, Mitchell KE, Ganta S, Gilmour RF, Freeman LC. (2002) Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart. Am. J. Physiol. Heart Circ. Physiol.283 (1): H126-38. [PMID:12063283]

18. Furlan F, Guasti L, Avossa D, Becchetti A, Cilia E, Ballerini L, Arcangeli A. (2005) Interneurons transiently express the ERG K+ channels during development of mouse spinal networks in vitro. Neuroscience135 (4): 1179-92. [PMID:16165280]

19. Furlan F, Taccola G, Grandolfo M, Guasti L, Arcangeli A, Nistri A, Ballerini L. (2007) ERG conductance expression modulates the excitability of ventral horn GABAergic interneurons that control rhythmic oscillations in the developing mouse spinal cord. J. Neurosci.27 (4): 919-28. [PMID:17251434]

20. Gerlach AC, Stoehr SJ, Castle NA. (2010) Pharmacological removal of human ether-à-go-go-related gene potassium channel inactivation by 3-nitro-N-(4-phenoxyphenyl) benzamide (ICA-105574). Mol. Pharmacol.77 (1): 58-68. [PMID:19805508]

21. Gessner G, Macianskiene R, Starkus JG, Schönherr R, Heinemann SH. (2010) The amiodarone derivative KB130015 activates hERG1 potassium channels via a novel mechanism. Eur. J. Pharmacol.632 (1-3): 52-9. [PMID:20097192]

22. Gessner G, Zacharias M, Bechstedt S, Schönherr R, Heinemann SH. (2004) Molecular determinants for high-affinity block of human EAG potassium channels by antiarrhythmic agents. Mol. Pharmacol.65 (5): 1120-9. [PMID:15102940]

23. Gong Q, Zhang L, Vincent GM, Horne BD, Zhou Z. (2007) Nonsense mutations in hERG cause a decrease in mutant mRNA transcripts by nonsense-mediated mRNA decay in human long-QT syndrome. Circulation116 (1): 17-24. [PMID:17576861]

24. Gordon E, Lozinskaya IM, Lin Z, Semus SF, Blaney FE, Willette RN, Xu X. (2008) 2-[2-(3,4-dichloro-phenyl)-2,3-dihydro-1H-isoindol-5-ylamino]-nicotinic acid (PD-307243) causes instantaneous current through human ether-a-go-go-related gene potassium channels. Mol. Pharmacol.73 (3): 639-51. [PMID:18042732]

25. Gordon E, Panaghie G, Deng L, Bee KJ, Roepke TK, Krogh-Madsen T, Christini DJ, Ostrer H, Basson CT, Chung W, Abbott GW. (2008) A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance. Cardiovasc. Res.77 (1): 98-106. [PMID:18006462]

26. Guasti L, Cilia E, Crociani O, Hofmann G, Polvani S, Becchetti A, Wanke E, Tempia F, Arcangeli A. (2005) Expression pattern of the ether-a-go-go-related (ERG) family proteins in the adult mouse central nervous system: evidence for coassembly of different subunits. J. Comp. Neurol.491 (2): 157-74. [PMID:16127690]

27. Guo J, Wang T, Li X, Shallow H, Yang T, Li W, Xu J, Fridman MD, Yang X, Zhang S. (2012) Cell surface expression of human ether-a-go-go-related gene (hERG) channels is regulated by caveolin-3 protein via the ubiquitin ligase Nedd4-2. J. Biol. Chem.287 (40): 33132-41. [PMID:22879586]

28. Hansen RS, Diness TG, Christ T, Demnitz J, Ravens U, Olesen SP, Grunnet M. (2006) Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643). Mol. Pharmacol.69 (1): 266-77. [PMID:16219910]

29. Hansen RS, Diness TG, Christ T, Wettwer E, Ravens U, Olesen SP, Grunnet M. (2006) Biophysical characterization of the new human ether-a-go-go-related gene channel opener NS3623 [N-(4-bromo-2-(1H-tetrazol-5-yl)-phenyl)-N'-(3'-trifluoromethylphenyl)urea]. Mol. Pharmacol.70 (4): 1319-29. [PMID:16825484]

30. Herzberg IM, Trudeau MC, Robertson GA. (1998) Transfer of rapid inactivation and sensitivity to the class III antiarrhythmic drug E-4031 from HERG to M-eag channels. J. Physiol. (Lond.)511 ( Pt 1): 3-14. [PMID:9679158]

31. Hill AP, Sunde M, Campbell TJ, Vandenberg JI. (2007) Mechanism of block of the hERG K+ channel by the scorpion toxin CnErg1. Biophys. J.92 (11): 3915-29. [PMID:17369411]

32. Huffaker SJ, Chen J, Nicodemus KK, Sambataro F, Yang F, Mattay V, Lipska BK, Hyde TM, Song J, Rujescu D et al.. (2009) A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia. Nat. Med.15 (5): 509-18. [PMID:19412172]

33. Jones EM, Roti Roti EC, Wang J, Delfosse SA, Robertson GA. (2004) Cardiac IKr channels minimally comprise hERG 1a and 1b subunits. J. Biol. Chem.279 (43): 44690-4. [PMID:15304481]

34. Kang J, Chen XL, Wang H, Ji J, Cheng H, Incardona J, Reynolds W, Viviani F, Tabart M, Rampe D. (2005) Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel. Mol. Pharmacol.67 (3): 827-36. [PMID:15548764]

35. Keserü GM. (2003) Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg. Med. Chem. Lett.13 (16): 2773-5. [PMID:12873512]

36. Kirchberger NM, Wulfsen I, Schwarz JR, Bauer CK. (2006) Effects of TRH on heteromeric rat erg1a/1b K+ channels are dominated by the rerg1b subunit. J. Physiol. (Lond.)571 (Pt 1): 27-42. [PMID:16339175]

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Michael C. Sanguinetti, K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Bernardo Rudy, Walter Stühmer, Xiaoliang Wang.
Voltage-gated potassium channels: Kv11.1. Last modified on 24/01/2017. Accessed on 26/09/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=572.