Nomenclature: Kv7.2

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. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 872 20q13.3 KCNQ2 potassium voltage-gated channel, KQT-like subfamily, member 2 22
Mouse 6 1 870 2 H3-4 Kcnq2 potassium voltage-gated channel, subfamily Q, member 2 16
Rat 6 1 852 3q43 Kcnq2 potassium voltage-gated channel, KQT-like subfamily, member 2 11
Previous and Unofficial Names
KQT2
Kv7.2
KCNQ2
EBN
EBN1
ENB1
BFNC
KCNA11
HNSPC
KQT-like 2
potassium channel subunit alpha KvLQT2
potassium voltage-gated channel subfamily KQT member 2
potassium voltage-gated channel, KQT-like subfamily, member 2
potassium voltage-gated channel, subfamily Q, member 2
voltage-gated potassium channel subunit Kv7.2
Nmf134
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
KCNQ3 10,20,27
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Functional Characteristics
M current
Ion Selectivity and Conductance
Species:  Human
Single channel conductance (pS):  6.2
References:  13,24
Ion Selectivity and Conductance Comments
  • human KCNQ2 ion selectivity ranking: K+ > Rb+ > Cs+ > Na+ [3]
  • human KCNQ2/3 permeation sequence: Tl+ > K+ > Rb+ > NH4+ > Cs+ > Na+ [18]
  • human KCNQ2/3 conduction sequence: K+ > Tl+ > NH4+ ~ Rb+ > Cs+ [18]
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -37.0 – -40.0 132.0 3,14,19 Xenopus laevis oocyte Human
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -11.5 – -40.0 129.0 8,24-25 CHO cells Human
Inactivation  - -
Associated subunits (Human)
minK
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
zinc pyrithione Hs - 5.8 pEC50 - - 30
pEC50 5.8 [30]
retigabine Hs - 5.6 pEC50 - - 25
pEC50 5.6 (EC50 2.5x10-6 M) [25]
N-(S)-MPEPAamide Hs - 5.5 pEC50 - - 2,29
pEC50 5.5 [2,29]
flupirtine Hs - 5.0 pEC50 - - 15
pEC50 5.0 [15]
BMS204352 Hs - 5.0 pEC50 - - 21
pEC50 5.0 [21]
PIP2 Hs - 3.7 pEC50 - - 12
pEC50 3.7 [12]
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
XE991 Hs - 6.15 pIC50 - - 27
pIC50 6.15 [27]
L735821 Hs - 5.8 pIC50 - - 26
pIC50 5.8 [26]
tetraethylammonium Hs - 3.9 – 3.5 (median: 3.8) pIC50 - - 9,27-28
pIC50 3.9 – 3.5 (median: 3.8) [9,27-28]
linopirdine Hs - 5.32 - - - 27
5.32 [27]
Tissue Distribution
Predominantly expressed in brain
Species:  Human
Technique:  Northern Blot
References:  20,31
Cortex, hippocampus
Species:  Human
Technique:  Immunohistochemistry
References:  5
Basal ganglia, septum, thalamus, hippocampus (wide brain distribution)
Species:  Mouse
Technique:  Immunohistochemistry
References:  6
Sympathetic ganglia, high expression levels in the cerebellum, cortex and hippocampus
Species:  Rat
Technique:  Northern Blot
References:  27
Broad distribution in brain
Species:  Rat
Technique:  In situ hybridisation
References:  20
Physiological Functions
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current
Species:  Human
Tissue:  neurons
References:  5,20,27
Immunoreactivity in some terminal fields for KCNQ2, but not KCNQ3, suggests a presynaptic role in the regulation of action potential propagation and neurotransmitter release
Species:  Human
Tissue:  Brain and CNS
References:  5
KCNQ2 channels (as part of the M current) have been involved in neuronal excitability, resonance and behavior
Species:  Mouse
Tissue:  brain
References:  17
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnq2tm1Dgen Kcnq2tm1Dgen/Kcnq2tm1Dgen
B6.129P2-Kcnq2/J
MGI:1309503  MP:0003412 abnormal afterhyperpolarization PMID: 19060215 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1309503  MP:0004811 abnormal neuron physiology PMID: 18483067 
Kcnq2Nmf134 Kcnq2Nmf134/Kcnq2Nmf134
C57BL/6J
MGI:1309503  MP:0001650 abnormal seizure response to electrical stimulation
Kcnq2+|Kcnq2Nmf134 Kcnq2Nmf134/Kcnq2+
C57BL/6J
MGI:1309503  MP:0001650 abnormal seizure response to electrical stimulation
Kcnq2+|Kcnq2Nmf134 Kcnq2Nmf134/Kcnq2+
C57BL/6J-Kcnq2
MGI:1309503  MP:0001650 abnormal seizure response to electrical stimulation PMID: 16464983 
Kcnq2+|Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1309503  MP:0001650 abnormal seizure response to electrical stimulation PMID: 18483067 
Kcnq2tm1Hsa Kcnq2tm1Hsa/Kcnq2tm1Hsa
involves: 129P2/OlaHsd * C57BL/6
MGI:1309503  MP:0001177 atelectasis PMID: 10854243 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
B6.129-Kcnq2
MGI:1309503  MP:0001265 decreased body size PMID: 18483067 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
FVB.129-Kcnq2
MGI:1309503  MP:0001265 decreased body size PMID: 18483067 
Kcnq2+|Kcnq2tm1Dgen Kcnq2tm1Dgen/Kcnq2+
B6.129P2-Kcnq2/J
MGI:1309503  MP:0009142 decreased prepulse inhibition PMID: 20592205 
Kcnq2+|Kcnq2tm1Hsa Kcnq2tm1Hsa/Kcnq2+
involves: 129P2/OlaHsd * C57BL/6
MGI:1309503  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 10854243 
Kcnq2+|Kcnq2tm1Dgen Kcnq2tm1Dgen/Kcnq2+
involves: 129P2/OlaHsd * C57BL/6
MGI:1309503  MP:0002906 increased susceptibility to pharmacologically induced seizures
Kcnq2+|Kcnq2Nmf134 Kcnq2Nmf134/Kcnq2+
C57BL/6J-Kcnq2
MGI:1309503  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 16464983 
Kcnq2tm1Hsa Kcnq2tm1Hsa/Kcnq2tm1Hsa
involves: 129P2/OlaHsd * C57BL/6
MGI:1309503  MP:0002058 neonatal lethality PMID: 10854243 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
B6.129-Kcnq2
MGI:1309503  MP:0002058 neonatal lethality PMID: 18483067 
Kcnq2tm1Dgen Kcnq2tm1Dgen/Kcnq2tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:1309503  MP:0002082 postnatal lethality
Kcnq2+|Kcnq2Nmf134|Tg(Eno2-Scn2a1*)Q54Mm Kcnq2Nmf134/Kcnq2+,Tg(Eno2-Scn2a1*)Q54Mm/0
involves: C57BL/6J * SJL/J
MGI:1309503  MGI:3793790  MP:0002082 postnatal lethality PMID: 16464983 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1309503  MP:0002082 postnatal lethality PMID: 18483067 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
FVB.129-Kcnq2
MGI:1309503  MP:0002082 postnatal lethality PMID: 18483067 
Kcnq2+|Kcnq2Nmf134|Tg(Eno2-Scn2a1*)Q54Mm Kcnq2Nmf134/Kcnq2+,Tg(Eno2-Scn2a1*)Q54Mm/0
involves: C57BL/6J * SJL/J
MGI:1309503  MGI:3793790  MP:0002083 premature death PMID: 16464983 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
B6.129-Kcnq2
MGI:1309503  MP:0002083 premature death PMID: 18483067 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
FVB.129-Kcnq2
MGI:1309503  MP:0002083 premature death PMID: 18483067 
Kcnq2+|Kcnq2Nmf134|Tg(Eno2-Scn2a1*)Q54Mm Kcnq2Nmf134/Kcnq2+,Tg(Eno2-Scn2a1*)Q54Mm/0
involves: C57BL/6J * SJL/J
MGI:1309503  MGI:3793790  MP:0002064 seizures PMID: 16464983 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1309503  MP:0002064 seizures PMID: 18483067 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
FVB.129-Kcnq2
MGI:1309503  MP:0002064 seizures PMID: 18483067 
Kcnq2+|Kcnq2Nmf134|Tg(Eno2-Scn2a1*)Q54Mm Kcnq2Nmf134/Kcnq2+,Tg(Eno2-Scn2a1*)Q54Mm/0
involves: C57BL/6J * SJL/J
MGI:1309503  MGI:3793790  MP:0003997 tonic-clonic seizures PMID: 16464983 
Kcnq2tm1.1Naas Kcnq2tm1.1Naas/Kcnq2tm1.1Naas
B6.129-Kcnq2
MGI:1309503  MP:0003997 tonic-clonic seizures PMID: 18483067 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Myokymia with neonatal epilepsy
OMIM:  606437
Role: 
Comments: 
References:  7
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human R207W ( in the S4 Voltage sensor segment) 7
Disease:  Epileptic encephalopathy, early infantile, 7; EIEE7
OMIM:  613720
Orphanet:  1934
References: 
Mutations not determined
Disease:  Benign familial infantile seizures
Orphanet:  306
References: 
Mutations not determined
Disease:  Benign familial neonatal convulsions type 1 (BFNC1); also known as epilepsy, benign neonatal type 1 (EBN1)
OMIM:  121200
Orphanet:  1949
Role: 
Drugs: 
Side effects:  Retigabine: chills, pain, symptomatic hypotension, dizziness, nausea, myalgia, sweating, vomiting, asthenia and somnolence. Flupirtine: drowsiness, dizziness, dry mouth, pruritis and nausea
Therapeutic use:  Retigabine and flupirtine have shown antiepileptic activity in humans and in a broad range of seizure models in rodents. Retigabine and flupirtine may possess actions unrelated to KCNQ opening. It is unclear, therefore, if the efficacy of retigabine and flupirtine in animals models of epilepsy and pain and in human studies is entirely due to KCNQ activation.
Comments: 
References:  1,3-4,22
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human 3
Missense Human several 22
Disease:  Benign familial neonatal-infantile seizures
Orphanet:  140927
References: 
Mutations not determined
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  Isoform 2 is preferentially expressed in differentiated neurons
Amino acids:  872
Protein accession: 
References:  23
Type:  Splice variant
Species:  Human
Description:  soform 6 expression is prominent in fetal brain, undifferentiated neuroblastoma cells, and brain tumors
Amino acids:  13
Protein accession: 
References:  23
General Comments
The M current is a slowly activating and deactivating potassium conductance that plays a critical role in determining the sub-threshold excitability of neurones as well as the responsiveness to synaptic inputs. The M current was first described in peripheral sympathetic neurones, and differential expression of this conductance produces subtypes of sympathetic neurones with distinct firing patterns. The M current is also expressed in many neurons in the central nervous system. The M-current is mediated by members of the Kv7 family, which form a heterotetrameric channel consisting of KCNQ3 subunits associated with either KCNQ2 or KCNQ5 subunits. Expression of KCNQ2, KCNQ3 and KCNQ5 proteins mostly overlaps with distribution of M current.

REFERENCES

1. Abbott GW, Butler MH, Bendahhou S, Dalakas MC, Ptacek LJ, Goldstein SA. (2001) MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell104 (2): 217-31. [PMID:11207363]

2. Bentzen BH, Schmitt N, Calloe K, Dalby Brown W, Grunnet M, Olesen SP. (2006) The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology51 (6): 1068-77. [PMID:16904708]

3. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK. (1998) A potassium channel mutation in neonatal human epilepsy. Science279 (5349): 403-6. [PMID:9430594]

4. Coghlan MJ, Carroll WA, Gopalakrishnan M. (2001) Recent developments in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress. J. Med. Chem.44 (11): 1627-53. [PMID:11356099]

5. Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, Jan LY. (2000) Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc. Natl. Acad. Sci. U.S.A.97 (9): 4914-9. [PMID:10781098]

6. Cooper EC, Harrington E, Jan YN, Jan LY. (2001) M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain. J. Neurosci.21 (24): 9529-40. [PMID:11739564]

7. Dedek K, Kunath B, Kananura C, Reuner U, Jentsch TJ, Steinlein OK. (2001) Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel. Proc. Natl. Acad. Sci. U.S.A.98 (21): 12272-7. [PMID:11572947]

8. Gamper N, Stockand JD, Shapiro MS. (2003) Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase. J. Neurosci.23 (1): 84-95. [PMID:12514204]

9. Hadley JK, Noda M, Selyanko AA, Wood IC, Abogadie FC, Brown DA. (2000) Differential tetraethylammonium sensitivity of KCNQ1-4 potassium channels. Br. J. Pharmacol.129 (3): 413-5. [PMID:10711337]

10. Hadley JK, Passmore GM, Tatulian L, Al-Qatari M, Ye F, Wickenden AD, Brown DA. (2003) Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium. J. Neurosci.23 (12): 5012-9. [PMID:12832524]

11. Jow F, Wang K. (2000) Cloning and functional expression of rKCNQ2 K(+) channel from rat brain. Brain Res. Mol. Brain Res.80 (2): 269-78. [PMID:11038262]

12. Li Y, Gamper N, Hilgemann DW, Shapiro MS. (2005) Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J. Neurosci.25 (43): 9825-35. [PMID:16251430]

13. Li Y, Gamper N, Shapiro MS. (2004) Single-channel analysis of KCNQ K+ channels reveals the mechanism of augmentation by a cysteine-modifying reagent. J. Neurosci.24 (22): 5079-90. [PMID:15175377]

14. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA. (2000) Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol. Pharmacol.58 (2): 253-62. [PMID:10908292]

15. Martire M, Castaldo P, D'Amico M, Preziosi P, Annunziato L, Taglialatela M. (2004) M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals. J. Neurosci.24 (3): 592-7. [PMID:14736843]

16. McCormack T, Rudy B, Seldin MF. (1999) Chromosomal mapping of the potassium channel genes Kcnq2 and Kcnq3 in mouse. Genomics56 (3): 360-1. [PMID:10087209]

17. Peters HC, Hu H, Pongs O, Storm JF, Isbrandt D. (2005) Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior. Nat. Neurosci.8 (1): 51-60. [PMID:15608631]

18. Prole DL, Marrion NV. (2004) Ionic permeation and conduction properties of neuronal KCNQ2/KCNQ3 potassium channels. Biophys. J.86 (3): 1454-69. [PMID:14990473]

19. Schenzer A, Friedrich T, Pusch M, Saftig P, Jentsch TJ, Grötzinger J, Schwake M. (2005) Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine. J. Neurosci.25 (20): 5051-60. [PMID:15901787]

20. Schroeder BC, Kubisch C, Stein V, Jentsch TJ. (1998) Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature396 (6712): 687-90. [PMID:9872318]

21. Schrøder RL, Jespersen T, Christophersen P, Strøbaek D, Jensen BS, Olesen SP. (2001) KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology40 (7): 888-98. [PMID:11378159]

22. Singh NA, Charlier C, Stauffer D, DuPont BR, Leach RJ, Melis R, Ronen GM, Bjerre I, Quattlebaum T, Murphy JV, McHarg ML, Gagnon D, Rosales TO, Peiffer A, Anderson VE, Leppert M. (1998) A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat. Genet.18 (1): 25-9. [PMID:9425895]

23. Smith JS, Iannotti CA, Dargis P, Christian EP, Aiyar J. (2001) Differential expression of kcnq2 splice variants: implications to m current function during neuronal development. J. Neurosci.21 (4): 1096-103. [PMID:11160379]

24. Soldovieri MV, Cilio MR, Miceli F, Bellini G, Miraglia del Giudice E, Castaldo P, Hernandez CC, Shapiro MS, Pascotto A, Annunziato L, Taglialatela M. (2007) Atypical gating of M-type potassium channels conferred by mutations in uncharged residues in the S4 region of KCNQ2 causing benign familial neonatal convulsions. J. Neurosci.27 (18): 4919-28. [PMID:17475800]

25. Tatulian L, Delmas P, Abogadie FC, Brown DA. (2001) Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine. J. Neurosci.21 (15): 5535-45. [PMID:11466425]

26. Tinel N, Lauritzen I, Chouabe C, Lazdunski M, Borsotto M. (1998) The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3. FEBS Lett.438 (3): 171-6. [PMID:9827540]

27. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D. (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science282 (5395): 1890-3. [PMID:9836639]

28. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK. (2000) Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol. Pharmacol.58 (3): 591-600. [PMID:10953053]

29. Wu YJ, Boissard CG, Greco C, Gribkoff VK, Harden DG, He H, L'Heureux A, Kang SH, Kinney GG, Knox RJ, Natale J, Newton AE, Lehtinen-Oboma S, Sinz MW, Sivarao DV, Starrett JE, Sun LQ, Tertyshnikova S, Thompson MW, Weaver D, Wong HS, Zhang L, Dworetzky SI. (2003) (S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide: an orally bioavailable KCNQ2 opener with significant activity in a cortical spreading depression model of migraine. J. Med. Chem.46 (15): 3197-200. [PMID:12852750]

30. Xiong Q, Sun H, Li M. (2007) Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat. Chem. Biol.3 (5): 287-96. [PMID:17435769]

31. Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, Blanar MA. (1998) Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. J. Biol. Chem.273 (31): 19419-23. [PMID:9677360]

To cite this database page, please use the following:

K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Bernardo Rudy, Michael C. Sanguinetti, Walter Stühmer, Xiaoliang Wang.
Voltage-gated potassium channels: Kv7.2. Last modified on 23/05/2014. Accessed on 01/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=561.

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