K<SUB>v</SUB>7.5 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

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Target not currently curated in GtoImmuPdb

Target id: 564

Nomenclature: Kv7.5

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

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 932 6q14 KCNQ5 potassium voltage-gated channel subfamily Q member 5 13
Mouse 6 1 933 1 A5 Kcnq5 potassium voltage-gated channel, subfamily Q, member 5 12
Rat 6 1 951 9q13 Kcnq5 potassium voltage-gated channel subfamily Q member 5
Previous and Unofficial Names
Kcnq5l | potassium channel, voltage gated KQT-like subfamily Q, member 5 | potassium channel, voltage-gated KQT-like subfamily Q, member 5 | potassium voltage-gated channel
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kv7.3 13,19
Kv7.4 1
Auxiliary Subunits
Name References
KCNE1 18
KCNE3 18
Other Associated Proteins
Name References
Calmodulin 10
Associated Protein Comments
KCNE1 and KCNE3 are auxiliary subunits in skeletal muscle [18].

Gating and modulation: Ca2+-calmodulin reduces the currents produced by KCNQ2, KCNQ4 and KCNQ5, but not those of KCNQ1 and KCNQ3 [6]. PIP2 stabilizes the channel in the open state [7,14]. In mesenteric artery smooth muscle cells, protein kinase C phosphorylates both KCNQ4 and KCNQ5 heteromers, thereby reducing the KCNQ4/KCNQ5 currents in response to vasoconstriction [3].
Functional Characteristics
M current as heteromeric KV7.3/KV7.5
Ion Selectivity and Conductance
Species:  Human
Single channel conductance (pS):  2.2
References:  15
Ion Selectivity and Conductance Comments
  • cation selectivity rank order: Rb+ ~ K+ > Cs+ > Na+ [19]
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -41.0 – -48.0 119.0 13 Xenopus laevis oocyte Human
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - 150.0 8 CHO cells Human
Inactivation  - -

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
gabapentin Hs Activation 8.7 pEC50 - - 16
pEC50 8.7 (EC50 1.9x10-9 M) [16]
flindokalner Hs - 5.6 pEC50 - - 5
pEC50 5.6 [5]
zinc pyrithione Hs - 5.0 pEC50 - - 23
pEC50 5.0 [23]
retigabine Hs - 5.0 pEC50 - - 5
pEC50 5.0 (EC50 1x10-5 M) [5]
(S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide Hs - - - - - 2
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
linopirdine Hs - 4.8 pKd - - 13
pKd 4.8 (Kd 1.6x10-5 M) [13]
XE991 Hs - 4.2 pIC50 - - 19
pIC50 4.2 (IC50 6.5x10-5 M) [19]
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
tetraethylammonium Hs - 1.1 – 1.5 pIC50 - - 13,19
pIC50 1.1 – 1.5 [13,19]
Tissue Distribution
Strongly expressed in brain and skeletal muscle. In brain, expressed in cerebral cortex, occipital pole, frontal lobe and temporal lobe. Lower levels in hippocampus and putamen. Low to undetectable levels in medulla, cerebellum and thalamus.
Species:  Human
Technique:  Northern Blot
References:  13,19
Brain (splice variant I), skeletal muscle (splice variant II and III)
Species:  Human
Technique:  RT-PCR
References:  19
KCNQ5 is expressed in vascular smooth muscle cells
Species:  Human
Technique:  Immunohistochemistry
References:  17
Neurons of the superior cervical ganglion. KCNQ5 is the primary KCNQ subunit expressed in C-fibers.
Species:  Rat
Technique:  In situ hybridisation
References:  19
Physiological Functions
Determines sub-threshold excitability of neurones. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current
Species:  Human
Tissue:  Neurones
References:  12-13,19
Regulates neuronal excitability. The KCNQ5 potassium channel mediates a component of the after hyperpolarization current in mouse hippocampal CA3 pyramidal neurons. KCNQ5 channels control resting properties and release probability of the calyx of Held synapse
Species:  Rat
Tissue:  Hippocampal neurons
References:  11,20,22
Inhibition of KCNQ5 channels increases action potential firing in aortic smooth muscle cells (A7r5 cells). KCNQ5 channels are regulators of the vascular smooth cell tone in veins and arteries.
Species:  Rat
Tissue:  Aortic smooth muscle
References:  4,21
Clinically-Relevant Mutations and Pathophysiology Comments
Dysfunction of the heteromeric KCNQ3/KCNQ5 potassium channel is associated with autism spectrum disorders [9].
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 [13,19].


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1. Bal M, Zhang J, Zaika O, Hernandez CC, Shapiro MS. (2008) Homomeric and heteromeric assembly of KCNQ (Kv7) K+ channels assayed by total internal reflection fluorescence/fluorescence resonance energy transfer and patch clamp analysis. J. Biol. Chem., 283 (45): 30668-76. [PMID:18786918]

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. Neuropharmacology, 51 (6): 1068-77. [PMID:16904708]

3. Brueggemann LI, Mackie AR, Cribbs LL, Freda J, Tripathi A, Majetschak M, Byron KL. (2014) Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels. J. Biol. Chem., 289 (4): 2099-111. [PMID:24297175]

4. Brueggemann LI, Moran CJ, Barakat JA, Yeh JZ, Cribbs LL, Byron KL. (2007) Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol., 292 (3): H1352-63. [PMID:17071736]

5. Dupuis DS, Schrøder RL, Jespersen T, Christensen JK, Christophersen P, Jensen BS, Olesen SP. (2002) Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352. Eur. J. Pharmacol., 437 (3): 129-37. [PMID:11890900]

6. Gamper N, Li Y, Shapiro MS. (2005) Structural requirements for differential sensitivity of KCNQ K+ channels to modulation by Ca2+/calmodulin. Mol. Biol. Cell, 16 (8): 3538-51. [PMID:15901836]

7. Gamper N, Shapiro MS. (2007) Regulation of ion transport proteins by membrane phosphoinositides. Nat. Rev. Neurosci., 8 (12): 921-34. [PMID:17971783]

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. Gilling M, Rasmussen HB, Calloe K, Sequeira AF, Baretto M, Oliveira G, Almeida J, Lauritsen MB, Ullmann R, Boonen SE et al.. (2013) Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders. Front Genet, 4: 54. [PMID:23596459]

10. Haitin Y, Attali B. (2008) The C-terminus of Kv7 channels: a multifunctional module. J. Physiol. (Lond.), 586 (7): 1803-10. [PMID:18218681]

11. Huang H, Trussell LO. (2011) KCNQ5 channels control resting properties and release probability of a synapse. Nat. Neurosci., 14 (7): 840-7. [PMID:21666672]

12. Jensen HS, Callø K, Jespersen T, Jensen BS, Olesen SP. (2005) The KCNQ5 potassium channel from mouse: a broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes. Brain Res. Mol. Brain Res., 139 (1): 52-62. [PMID:15963599]

13. Lerche C, Scherer CR, Seebohm G, Derst C, Wei AD, Busch AE, Steinmeyer K. (2000) Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M-current diversity. J. Biol. Chem., 275 (29): 22395-400. [PMID:10787416]

14. 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]

15. 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]

16. Manville RW, Abbott GW. (2018) Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels. Mol. Pharmacol., 94 (4): 1155-1163. [PMID:30021858]

17. Ng FL, Davis AJ, Jepps TA, Harhun MI, Yeung SY, Wan A, Reddy M, Melville D, Nardi A, Khong TK et al.. (2011) Expression and function of the K+ channel KCNQ genes in human arteries. Br. J. Pharmacol., 162 (1): 42-53. [PMID:20840535]

18. Roura-Ferrer M, Etxebarria A, Solé L, Oliveras A, Comes N, Villarroel A, Felipe A. (2009) Functional implications of KCNE subunit expression for the Kv7.5 (KCNQ5) channel. Cell. Physiol. Biochem., 24 (5-6): 325-34. [PMID:19910673]

19. Schroeder BC, Hechenberger M, Weinreich F, Kubisch C, Jentsch TJ. (2000) KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents. J. Biol. Chem., 275 (31): 24089-95. [PMID:10816588]

20. Shah M, Mistry M, Marsh SJ, Brown DA, Delmas P. (2002) Molecular correlates of the M-current in cultured rat hippocampal neurons. J. Physiol. (Lond.), 544 (Pt 1): 29-37. [PMID:12356878]

21. Stott JB, Jepps TA, Greenwood IA. (2014) K(V)7 potassium channels: a new therapeutic target in smooth muscle disorders. Drug Discov. Today, 19 (4): 413-24. [PMID:24333708]

22. Tzingounis AV, Heidenreich M, Kharkovets T, Spitzmaul G, Jensen HS, Nicoll RA, Jentsch TJ. (2010) The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus. Proc. Natl. Acad. Sci. U.S.A., 107 (22): 10232-7. [PMID:20534576]

23. 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]


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