KCNQ3

Summary

Gene Symbol: KCNQ3
Description: potassium voltage-gated channel subfamily Q member 3
Alias: BFNC2, EBN2, KV7.3, potassium voltage-gated channel subfamily KQT member 3, potassium channel subunit alpha KvLQT3, potassium channel, voltage gated KQT-like subfamily Q, member 3, potassium channel, voltage-gated, subfamily Q, member 3, potassium voltage-gated channel, KQT-like subfamily, member 3, voltage-gated potassium channel subunit Kv7.3
Species: human
Products:     KCNQ3

Top Publications

  1. Kubisch C, Schroeder B, Friedrich T, Lütjohann B, El Amraoui A, Marlin S, et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell. 1999;96:437-46 pubmed
    ..Whereas mutations in KCNQ1 cause deafness by affecting endolymph secretion, the mechanism leading to KCNQ4-related hearing loss is intrinsic to outer hair cells. ..
  2. Gómez Posada J, Etxeberria A, Roura Ferrer M, Areso P, Masin M, Murrell Lagnado R, et al. A pore residue of the KCNQ3 potassium M-channel subunit controls surface expression. J Neurosci. 2010;30:9316-23 pubmed publisher
    KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) are the principal subunits underlying the potassium M-current, which exerts a strong control on neuronal excitability...
  3. Wang H, Pan Z, Shi W, Brown B, Wymore R, Cohen I, et al. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science. 1998;282:1890-3 pubmed
    ..The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current.
  4. Uehara A, Nakamura Y, Shioya T, Hirose S, Yasukochi M, Uehara K. Altered KCNQ3 potassium channel function caused by the W309R pore-helix mutation found in human epilepsy. J Membr Biol. 2008;222:55-63 pubmed publisher
    ..A missense mutation causing the replacement of the corresponding residues with an arginine (W309R) occurs in KCNQ3 subunits forming part of M-channels...
  5. Neubauer B, Waldegger S, Heinzinger J, Hahn A, Kurlemann G, Fiedler B, et al. KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes. Neurology. 2008;71:177-83 pubmed publisher
    ..An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting rolandic epilepsy and benign neonatal convulsions...
  6. Etzioni A, Siloni S, Chikvashvilli D, Strulovich R, Sachyani D, Regev N, et al. Regulation of neuronal M-channel gating in an isoform-specific manner: functional interplay between calmodulin and syntaxin 1A. J Neurosci. 2011;31:14158-71 pubmed publisher
    Whereas neuronal M-type K(+) channels composed of KCNQ2 and KCNQ3 subunits regulate firing properties of neurons, presynaptic KCNQ2 subunits were demonstrated to regulate neurotransmitter release by directly influencing presynaptic ..
  7. Yus Najera E, Santana Castro I, Villarroel A. The identification and characterization of a noncontinuous calmodulin-binding site in noninactivating voltage-dependent KCNQ potassium channels. J Biol Chem. 2002;277:28545-53 pubmed
    ..CaM co-immunoprecipitates with KCNQ2, KCNQ3, or KCNQ5 subunits better in the absence than in the presence of Ca2+...
  8. Schwake M, Jentsch T, Friedrich T. A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly. EMBO Rep. 2003;4:76-81 pubmed
    ..KCNQ1 assembles with KCNE beta-subunits but not with other KCNQ alpha-subunits. By contrast, KCNQ3 interacts with KCNQ2, KCNQ4 and KCNQ5...
  9. Etxeberria A, Santana Castro I, Regalado M, Aivar P, Villarroel A. Three mechanisms underlie KCNQ2/3 heteromeric potassium M-channel potentiation. J Neurosci. 2004;24:9146-52 pubmed
    ..Notably, in terms of excitation, mutations in either KCNQ2 or KCNQ3 lead to benign neonatal familial convulsions...

More Information

Publications114 found, 100 shown here

  1. Charlier C, Singh N, Ryan S, Lewis T, Reus B, Leach R, et al. A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet. 1998;18:53-5 pubmed
    ..Here we describe an additional member, KCNQ3. We mapped this new gene to chromosome 8, between markers D8S256 and D8S284 on a radiation hybrid map...
  2. Schroeder B, Kubisch C, Stein V, Jentsch T. Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature. 1998;396:687-90 pubmed
    ..neonatal convulsions (BFNC), an autosomal dominant epilepsy of infancy, is caused by mutations in the KCNQ2 or the KCNQ3 potassium channel genes...
  3. Schwake M, Pusch M, Kharkovets T, Jentsch T. Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. J Biol Chem. 2000;275:13343-8 pubmed
    Mutations in either KCNQ2 or KCNQ3 underlie benign familial neonatal convulsions (BFNC), an inherited epilepsy. The corresponding proteins are co-expressed in broad regions of the brain and associate to heteromeric K(+) channels...
  4. Wen H, Levitan I. Calmodulin is an auxiliary subunit of KCNQ2/3 potassium channels. J Neurosci. 2002;22:7991-8001 pubmed
    Calmodulin (CaM) was identified as a KCNQ2 and KCNQ3 potassium channel-binding protein, using a yeast two-hybrid screen...
  5. Chung H, Jan Y, Jan L. Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains. Proc Natl Acad Sci U S A. 2006;103:8870-5 pubmed
    ..Mutations in KCNQ2 and KCNQ3 cause benign familial neonatal convulsions (BFNC), dominantly inherited epilepsy and myokymia...
  6. Zaika O, Hernandez C, Bal M, Tolstykh G, Shapiro M. Determinants within the turret and pore-loop domains of KCNQ3 K+ channels governing functional activity. Biophys J. 2008;95:5121-37 pubmed publisher
    ..KCNQ1 and KCNQ4 homomers and KCNQ2/3 heteromers yield large currents, whereas KCNQ2 and KCNQ3 homomers yield small currents...
  7. Gómez Posada J, Aivar P, Alberdi A, Alaimo A, Etxeberria A, Fernandez Orth J, et al. Kv7 channels can function without constitutive calmodulin tethering. PLoS ONE. 2011;6:e25508 pubmed publisher
    ..However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function. ..
  8. Fidzinski P, Korotkova T, Heidenreich M, Maier N, Schuetze S, Kobler O, et al. KCNQ5 K(+) channels control hippocampal synaptic inhibition and fast network oscillations. Nat Commun. 2015;6:6254 pubmed publisher
    KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) K(+) channels dampen neuronal excitability and their functional impairment may lead to epilepsy. Less is known about KCNQ5 (Kv7.5), which also displays wide expression in the brain...
  9. Gourgy Hacohen O, Kornilov P, Pittel I, Peretz A, Attali B, Paas Y. Capturing distinct KCNQ2 channel resting states by metal ion bridges in the voltage-sensor domain. J Gen Physiol. 2014;144:513-27 pubmed publisher
    ..KCNQ2 can coassemble with the KCNQ3 subunit to mediate the IM current that regulates neuronal excitability...
  10. Manville R, Abbott G. Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels. Mol Pharmacol. 2018;94:1155-1163 pubmed publisher
    ..voltage-gated potassium channel, the primary molecular correlate of the neuronal M-current, and also homomeric KCNQ3 and KCNQ5 channels...
  11. Mills T, Greenwood S, Devlin G, Shweikh Y, Robinson M, Cowley E, et al. Activation of KV7 channels stimulates vasodilatation of human placental chorionic plate arteries. Placenta. 2015;36:638-44 pubmed publisher
    ..1 - Kv7.5 channels. All CPAs assessed expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs...
  12. Li H, Li N, Shen L, Jiang H, Yang Q, Song Y, et al. A novel mutation of KCNQ3 gene in a Chinese family with benign familial neonatal convulsions. Epilepsy Res. 2008;79:1-5 pubmed publisher
    ..Two voltage-gated potassium channel subunit genes, KCNQ2 and KCNQ3, have been identified to cause BFNC1 and BFNC2, respectively. To date, only three mutations of KCNQ3, all located within exon 5, have been reported...
  13. Mistry H, McCallum L, Kurlak L, Greenwood I, Broughton Pipkin F, Tribe R. Novel expression and regulation of voltage-dependent potassium channels in placentas from women with preeclampsia. Hypertension. 2011;58:497-504 pubmed publisher
    ..Protein expression/localization was assessed using immunohistochemistry. KCNQ3 and KCNE5 mRNA expressions were significantly upregulated in preeclampsia (median [interquartile range]: 1.942 [0...
  14. Mucha M, Ooi L, Linley J, Mordaka P, Dalle C, Robertson B, et al. Transcriptional control of KCNQ channel genes and the regulation of neuronal excitability. J Neurosci. 2010;30:13235-45 pubmed publisher
    ..2 and Kv7.3 play a key role in stabilizing neuronal activity. Mutations in KCNQ2 and KCNQ3, the genes encoding Kv7.2 and Kv7...
  15. Hamada M, Kole M. Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability. J Neurosci. 2015;35:7272-86 pubmed publisher
    ..These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons. ..
  16. Wang J, Li Y, Hui Z, Cao M, Shi R, Zhang W, et al. Functional analysis of potassium channels in Kv7.2 G271V mutant causing early onset familial epilepsy. Brain Res. 2015;1616:112-22 pubmed publisher
  17. Wang A, Yau M, Wang C, Sharmin N, Yang R, Pless S, et al. Four drug-sensitive subunits are required for maximal effect of a voltage sensor-targeted KCNQ opener. J Gen Physiol. 2018;: pubmed publisher
    ..in this issue), we demonstrate very different stoichiometry for the action of retigabine on KCNQ3, for which a single retigabine-sensitive subunit enables near-maximal effect...
  18. O Donnell A, Coyle D, Puri P. Decreased expression of Kv7 channels in Hirchsprung's disease. J Pediatr Surg. 2017;52:1177-1181 pubmed publisher
    ..A deficiency of Kv7.4 channels in the ganglionic and aganglionic bowel may place a role in colonic dysmotility in HSCR. ..
  19. Guo J, Schofield G. Histamine inhibits KCNQ2/KCNQ3 channel current via recombinant histamine H(1) receptors. Neurosci Lett. 2002;328:285-8 pubmed
    ..Expression of KCNQ2 and KCNQ3 K(+) channel subunits by transient transfection in HEK 293T and HeLa cells caused the induction of a slow time-..
  20. Miceli F, Striano P, Soldovieri M, Fontana A, Nardello R, Robbiano A, et al. A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability. Epilepsia. 2015;56:e15-20 pubmed publisher
    ..By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS...
  21. Wickenden A, McNaughton Smith G. Kv7 channels as targets for the treatment of pain. Curr Pharm Des. 2009;15:1773-98 pubmed
    ..x as drug targets for the treatment of pain. In addition, an update on pre-clinical Kv7 drug discovery efforts will be presented, along with a summary of on-going clinical trials with Kv7 channel activators. ..
  22. Hansen H, Weikop P, Mikkelsen M, Rode F, Mikkelsen J. The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo. Basic Clin Pharmacol Toxicol. 2017;120:46-51 pubmed publisher
    ..The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo. ..
  23. Bosch D, Boonstra F, de Leeuw N, Pfundt R, Nillesen W, de Ligt J, et al. Novel genetic causes for cerebral visual impairment. Eur J Hum Genet. 2016;24:660-5 pubmed publisher
    ..one or more candidate genes were identified (ACP6, AMOT, ARHGEF10L, ATP6V1A, DCAF6, DLG4, GABRB2, GRIN1, GRIN2B, KCNQ3, KCTD19, RERE, SLC1A1, SLC25A16, SLC35A2, SOX5, UFSP2, UHMK1, ZFP30)...
  24. Choveau F, Zhang J, Bierbower S, Sharma R, Shapiro M. The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K+ Current Amplitudes by Controlling Channel Trafficking. PLoS ONE. 2015;10:e0145367 pubmed publisher
    In the central and peripheral nervous system, the assembly of KCNQ3 with KCNQ2 as mostly heteromers, but also homomers, underlies "M-type" currents, a slowly-activating voltage-gated K+ current that plays a dominant role in neuronal ..
  25. Baulac S, Baulac M. Advances on the genetics of mendelian idiopathic epilepsies. Neurol Clin. 2009;27:1041-1061 pubmed publisher
    ..strategies in multi-generational families with autosomal dominant transmission have revealed 11 genes (KCNQ2, KCNQ3, CHRNA4, CHRNA2, CHRNB2, SCN1B, SCN1A, SCN2A, GABRG2, GABRA1, and LGI1) and numerous loci for febrile seizures and ..
  26. Maljevic S, Lerche H. Potassium channel genes and benign familial neonatal epilepsy. Prog Brain Res. 2014;213:17-53 pubmed publisher
    ..Among them, KCNQ2 and KCNQ3, coding for KV7.2 and KV7...
  27. Li C, Huang P, Lu Q, Zhou M, Guo L, Xu X. KCNQ/Kv7 channel activator flupirtine protects against acute stress-induced impairments of spatial memory retrieval and hippocampal LTP in rats. Neuroscience. 2014;280:19-30 pubmed publisher
    ..Acute stress transiently decreased the expression of KCNQ2 and KCNQ3 in the hippocampus...
  28. Schütze S, Orozco I, Jentsch T. KCNQ Potassium Channels Modulate Sensitivity of Skin Down-hair (D-hair) Mechanoreceptors. J Biol Chem. 2016;291:5566-75 pubmed publisher
    ..play an important role in regulating the excitability of neuronal cells, as highlighted by mutations in Kcnq2 and Kcnq3 that underlie certain forms of epilepsy...
  29. Ihara Y, Tomonoh Y, Deshimaru M, Zhang B, Uchida T, Ishii A, et al. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations. PLoS ONE. 2016;11:e0150095 pubmed publisher
    The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7...
  30. Devaux J, Abidi A, Roubertie A, Molinari F, Becq H, Lacoste C, et al. A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity. Epilepsia. 2016;57:e87-93 pubmed publisher
    ..These findings alert us that drugs aiming to increase Kv7 channel activity might have adverse effects in EOEE in the case of gain-of-function variants. ..
  31. Kothur K, Holman K, Farnsworth E, Ho G, Lorentzos M, Troedson C, et al. Diagnostic yield of targeted massively parallel sequencing in children with epileptic encephalopathy. Seizure. 2018;59:132-140 pubmed publisher
    ..variants were found in ALDH7A1 (2), CACNA1A (1), CDKL5 (3), FOXG1 (2), GABRB3 (1), GRIN2A (1), KCNQ2 (4), KCNQ3 (1), PRRT2 (1), SCN1A (6), SCN2A (2), SCN8A (2), SYNGAP1 (1), UBE3A (2) and WWOX (1) genes...
  32. Siloni S, Singer Lahat D, Esa M, Tsemakhovich V, Chikvashvili D, Lotan I. Regulation of the neuronal KCNQ2 channel by Src--a dual rearrangement of the cytosolic termini underlies bidirectional regulation of gating. J Cell Sci. 2015;128:3489-501 pubmed publisher
    Neuronal M-type K(+) channels are heteromers of KCNQ2 and KCNQ3 subunits, and are found in cell bodies, dendrites and the axon initial segment, regulating the firing properties of neurons...
  33. Kim K, Rutherford M. Maturation of NaV and KV Channel Topographies in the Auditory Nerve Spike Initiator before and after Developmental Onset of Hearing Function. J Neurosci. 2016;36:2111-8 pubmed publisher
  34. Ambrosino P, Freri E, Castellotti B, Soldovieri M, Mosca I, Manocchio L, et al. Kv7.3 Compound Heterozygous Variants in Early Onset Encephalopathy Reveal Additive Contribution of C-Terminal Residues to PIP2-Dependent K+ Channel Gating. Mol Neurobiol. 2018;55:7009-7024 pubmed publisher
    ..By contrast, only few mutations in the closely related Kv7.3 (KCNQ3) gene have been reported, mostly associated with typical benign familial neonatal seizures (BFNS)...
  35. Neverisky D, Abbott G. KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk. FASEB J. 2017;31:2828-2838 pubmed publisher
    Voltage-gated potassium channels formed by KCNQ2 and KCNQ3 are essential for normal neuronal excitability...
  36. Shellhaas R, Wusthoff C, Tsuchida T, Glass H, Chu C, Massey S, et al. Profile of neonatal epilepsies: Characteristics of a prospective US cohort. Neurology. 2017;89:893-899 pubmed publisher
    ..Six infants with BFNE had genetic testing; 3 had pathogenic KCNQ2 variants and 1 had a pathogenic KCNQ3 variant...
  37. Delgado Ramírez M, Sánchez Armass S, Meza U, Rodríguez Menchaca A. Regulation of Kv7.2/Kv7.3 channels by cholesterol: Relevance of an optimum plasma membrane cholesterol content. Biochim Biophys Acta Biomembr. 2018;1860:1242-1251 pubmed publisher
    ..In summary, our results indicate that an optimum cholesterol level in the plasma membrane is required for the proper functioning of Kv7.2/Kv7.3 channels. ..
  38. Suh B, Hille B. Does diacylglycerol regulate KCNQ channels?. Pflugers Arch. 2006;453:293-301 pubmed
    ..We test whether diacylglycerols are also important in the regulation of KCNQ2/KCNQ3 channels using electrophysiology and fluorescent translocation probes as indicators for PIP(2) and diacylglycerol ..
  39. Benned Jensen T, Christensen R, Denti F, Perrier J, Rasmussen H, Olesen S. Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed. J Neurosci. 2016;36:2261-6 pubmed publisher
    ..However, at high glutamate loads, they undergo a rapid calpain-dependent endocytosis that likely represents an early response during excitotoxic states. ..
  40. Manohar S, Dahar K, Adler H, Dalian D, Salvi R. Noise-induced hearing loss: Neuropathic pain via Ntrk1 signaling. Mol Cell Neurosci. 2016;75:101-12 pubmed publisher
    ..array, noise exposure upregulated mRNA expression levels of four pain/inflammatory genes, Tlr2, Oprd1, Kcnq3 and Ntrk1 and decreased mRNA expression levels of two more genes, Ccl12 and Il1?...
  41. Singh N, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, et al. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain. 2003;126:2726-37 pubmed
    ..Previously our laboratory cloned two novel potassium channel genes, KCNQ2 and KCNQ3, and showed that they are mutated in patients with BFNC...
  42. Zhou J, Gao Y, Kosten T, Zhao Z, Li D. Acute stress diminishes M-current contributing to elevated activity of hypothalamic-pituitary-adrenal axis. Neuropharmacology. 2017;114:67-76 pubmed publisher
    ..Collectively, these data suggest that acute stress diminishes Kv7 channels to stimulate PVN-CRH neurons and the HPA axis potentially via increased AMPK activity. ..
  43. Nyholt D, LaForge K, Kallela M, Alakurtti K, Anttila V, Farkkila M, et al. A high-density association screen of 155 ion transport genes for involvement with common migraine. Hum Mol Genet. 2008;17:3318-31 pubmed publisher
    ..SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (..
  44. Kim K, Duignan K, Hawryluk J, Soh H, Tzingounis A. The Voltage Activation of Cortical KCNQ Channels Depends on Global PIP2 Levels. Biophys J. 2016;110:1089-98 pubmed publisher
    ..Further, the sensitivity of this effect on KCNQ3 channels appeared to be higher than that on KCNQ2...
  45. Gomis Pèrez C, Soldovieri M, Malo C, Ambrosino P, Taglialatela M, Areso P, et al. Differential Regulation of PI(4,5)P2 Sensitivity of Kv7.2 and Kv7.3 Channels by Calmodulin. Front Mol Neurosci. 2017;10:117 pubmed publisher
    ..3 was unaltered. Altogether, the data reveal that apo-CaM influences PI(4,5)P2 dependence of Kv7.2, Kv7.2/3, and of Kv7.3 channels in a subunit specific manner. ..
  46. Wickenden A, Yu W, Zou A, Jegla T, Wagoner P. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000;58:591-600 pubmed
    ..Our findings identify KCNQ2/Q3 channels as a molecular target for retigabine and suggest that activation of KCNQ2/Q3 channels may be responsible for at least some of the anticonvulsant activity of this agent...
  47. Hadley J, Passmore G, Tatulian L, Al Qatari M, Ye F, Wickenden A, et al. Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium. J Neurosci. 2003;23:5012-9 pubmed
    KCNQ2 and KCNQ3 potassium-channel subunits can form both homomeric and heteromeric channels; the latter are thought to constitute native ganglionic M channels...
  48. Mistry H, Kurlak L, Whitley G, Cartwright J, Broughton Pipkin F, Tribe R. Expression of voltage-dependent potassium channels in first trimester human placentae. Placenta. 2014;35:337-40 pubmed publisher
    ..The aim was to determine KCNQ and KCNE mRNA expression and assess protein expression/localisation of the KCNQ3 and KCNE5 isoforms in first trimester placental tissue...
  49. Provence A, Malysz J, Petkov G. The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility. J Pharmacol Exp Ther. 2015;354:290-301 pubmed publisher
    ..In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels. ..
  50. Yang J, Song M, Shen Y, Ryu P, Lee S. The Role of KV7.3 in Regulating Osteoblast Maturation and Mineralization. Int J Mol Sci. 2016;17:407 pubmed publisher
    ..However, activation of KV7.3 by flupirtine did not produce notable changes in matrix mineralization during osteoblast differentiation. These results suggest that KV7.3 could be a novel regulator in osteoblast differentiation. ..
  51. Kim E, Zhang J, Pang W, Wang S, Lee K, Cavaretta J, et al. Reduced axonal surface expression and phosphoinositide sensitivity in Kv7 channels disrupts their function to inhibit neuronal excitability in Kcnq2 epileptic encephalopathy. Neurobiol Dis. 2018;118:76-93 pubmed publisher
    ..2/KCNQ2 and Kv7.3/KCNQ3 subunits. Enriched at the axonal membrane, they potently suppress neuronal excitability...
  52. Cavaliere S, Gillespie J, Hodge J. KCNQ channels show conserved ethanol block and function in ethanol behaviour. PLoS ONE. 2012;7:e50279 pubmed publisher
  53. Ambrosino P, Alaimo A, Bartollino S, Manocchio L, De Maria M, Mosca I, et al. Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin. Biochim Biophys Acta. 2015;1852:1856-66 pubmed publisher
    ..2 modulation as a potential therapeutic approach for Kv7.2-related epilepsies. ..
  54. Corbin Leftwich A, Mossadeq S, Ha J, Ruchala I, Le A, Villalba Galea C. Retigabine holds KV7 channels open and stabilizes the resting potential. J Gen Physiol. 2016;147:229-41 pubmed publisher
  55. Holt J, Jordan P, Lysakowski A, Shah A, Barsz K, Contini D. Muscarinic Acetylcholine Receptors and M-Currents Underlie Efferent-Mediated Slow Excitation in Calyx-Bearing Vestibular Afferents. J Neurosci. 2017;37:1873-1887 pubmed publisher
    ..Immunohistochemistry for putative M-current candidates suggested that turtle CD afferents express KCNQ3, KCNQ4, and ERG1-3 potassium channel subunits...
  56. Ryan S, Wiznitzer M, Hollman C, Torres M, Szekeresova M, Schneider S. Benign familial neonatal convulsions: evidence for clinical and genetic heterogeneity. Ann Neurol. 1991;29:469-73 pubmed
    ..We conclude that the syndrome of benign familial neonatal convulsions is clinically and genetically heterogeneous. Further study will be necessary to clarify the relationship between phenotype and genotype in this disorder. ..
  57. Sander S, Diwan M, Raymond R, Nobrega J, Richter A. Lower KV7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia. CNS Neurol Disord Drug Targets. 2016;15:95-101 pubmed
    ..5 channels. The experiments indicate a functional relevance for KV7.5 channels in paroxysmal dystonia. We suggest that compounds highly selective for subtypes of KV7 channels, i.e. for KV7.5, may provide new therapeutic approaches. ..
  58. Jepps T, Olesen S, Greenwood I, Dalsgaard T. Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats. Br J Pharmacol. 2016;173:1478-90 pubmed publisher
    ..Transcripts for KCNQ3, KCNQ4 and KCNQ5 were detected in penile arteries and corpus cavernosum. KCNQ1 was only found in corpus cavernosum...
  59. Di Cesare Mannelli L, Lucarini E, Micheli L, Mosca I, Ambrosino P, Soldovieri M, et al. Effects of natural and synthetic isothiocyanate-based H2S-releasers against chemotherapy-induced neuropathic pain: Role of Kv7 potassium channels. Neuropharmacology. 2017;121:49-59 pubmed publisher
    ..Sistemically- or centrally-administered isothiocyanates reduced chemotherapy-induced neuropathic pain by releasing H2S. Activation of Kv7 channels largely mediate the anti-neuropathic effect. ..
  60. Rundfeldt C, Netzer R. The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits. Neurosci Lett. 2000;282:73-6 pubmed
    ..Since the function of this channel is reduced in a hereditary epilepsy syndrome, retigabine may be the first anticonvulsant to directly target the deficit observed in a channelopathy...
  61. Lewis T, Leach R, Ward K, O Connell P, Ryan S. Genetic heterogeneity in benign familial neonatal convulsions: identification of a new locus on chromosome 8q. Am J Hum Genet. 1993;53:670-5 pubmed
    ..Multipoint analysis placed the BFNC locus in the interval spanned by D8S198-D8S274. This study establishes the presence of a new BFNC locus and confirms genetic heterogeneity of this disorder. ..
  62. Yus Najera E, Munoz A, Salvador N, Jensen B, Rasmussen H, Defelipe J, et al. Localization of KCNQ5 in the normal and epileptic human temporal neocortex and hippocampal formation. Neuroscience. 2003;120:353-64 pubmed
    ..Mutations in either KCNQ2 or KCNQ3 lead to a hereditary form of dominant generalized epilepsy...
  63. Pan Z, Kao T, Horvath Z, Lemos J, Sul J, Cranstoun S, et al. A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J Neurosci. 2006;26:2599-613 pubmed
    ..Here, antibodies against four different KCNQ2 and KCNQ3 polypeptide epitopes show these subunits concentrated at the axonal initial segment (AIS) and node of Ranvier...
  64. Wickenden A, Krajewski J, London B, Wagoner P, Wilson W, Clark S, et al. N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide (ICA-27243): a novel, selective KCNQ2/Q3 potassium channel activator. Mol Pharmacol. 2008;73:977-86 pubmed
    KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) are voltage-gated K(+) channel subunits that underlie the neuronal M current. In humans, mutations in these genes lead to a rare form of neonatal epilepsy (Biervert et al., 1998; Singh et al...
  65. Zara F, Specchio N, Striano P, Robbiano A, Gennaro E, Paravidino R, et al. Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance. Epilepsia. 2013;54:425-36 pubmed publisher
    ..SCN2A, KCNQ2, KCNQ3, PPRT2 point mutations were analyzed by direct sequencing of amplified genomic DNA...
  66. Kaminsky Z, Jones I, Verma R, Saleh L, Trivedi H, Guintivano J, et al. DNA methylation and expression of KCNQ3 in bipolar disorder. Bipolar Disord. 2015;17:150-9 pubmed publisher
    Accumulating evidence implicates the potassium voltage-gated channel, KQT-like subfamily, member 2 and 3 (KCNQ2 and KCNQ3) genes in the etiology of bipolar disorder (BPD)...
  67. Zhang Y, Chu X, Liu L, Zhang N, Guo H, Yang F, et al. Tannic acid activates the Kv7.4 and Kv7.3/7.5 K(+) channels expressed in HEK293 cells and reduces tension in the rat mesenteric arteries. J Pharm Pharmacol. 2016;68:494-502 pubmed publisher
    ..4 and Kv7.3/7.5 K(+) channels, which may be a mechanism to explain the vasodilatory effect and this mechanism can be used in the research of antihypertension. ..
  68. Surti T, Huang L, Jan Y, Jan L, Cooper E. Identification by mass spectrometry and functional characterization of two phosphorylation sites of KCNQ2/KCNQ3 channels. Proc Natl Acad Sci U S A. 2005;102:17828-33 pubmed
    ..the regulation of neuronal KCNQ channels, we searched directly for posttranslational modifications on KCNQ2/KCNQ3 channels in vivo by using mass spectrometry. Here we describe two sites of phosphorylation...
  69. Bal M, Zhang J, Zaika O, Hernandez C, Shapiro M. 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. 2008;283:30668-76 pubmed publisher
    ..b>KCNQ3 is widely thought to co-assemble with several other KCNQ subtypes, whereas KCNQ1 and KCNQ2 do not...
  70. Füll Y, Seebohm G, Lerche H, Maljevic S. A conserved threonine in the S1-S2 loop of KV7.2 and K V7.3 channels regulates voltage-dependent activation. Pflugers Arch. 2013;465:797-804 pubmed publisher
    ..This could be the explanation why substitution of the conserved threonine in KV7.2 and KV7.3 channels destabilizes the open and favors the closed state of these channels. ..
  71. Anta B, Martín Rodríguez C, Gomis Pèrez C, Calvo L, López Benito S, Calderón García A, et al. Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3). J Biol Chem. 2016;291:19132-45 pubmed publisher
    ..2/3 channel regulation. Our results demonstrate that USP36 binds to and regulates the actions of Nedd4-2 over different substrates affecting their expression and functions. ..
  72. Selyanko A, Hadley J, Wood I, Abogadie F, Jentsch T, Brown D. Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors. J Physiol. 2000;522 Pt 3:349-55 pubmed
    ..reduced (to 0-10%) currents produced by KCNQ1-4 subunits expressed individually and also those produced by KCNQ2 + KCNQ3 and KCNQ1 + KCNE1 heteromers, which are thought to generate neuronal M-currents (IK,M) and cardiac slow delayed ..
  73. Main M, Cryan J, Dupere J, Cox B, Clare J, Burbidge S. Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000;58:253-62 pubmed
    ..In the present study we have examined the effects of retigabine on recombinant human KCNQ2 and KCNQ3 potassium channels, expressed either alone or in combination in Xenopus oocytes...
  74. Maljevic S, Lerche C, Seebohm G, Alekov A, Busch A, Lerche H. C-terminal interaction of KCNQ2 and KCNQ3 K+ channels. J Physiol. 2003;548:353-60 pubmed
    Coexpression of KCNQ2 and KCNQ3 channels results in a 10-fold increased current amplitude compared to that of KCNQ2 alone, suggesting the formation of heteromultimeric channels. There is no interaction of either channel with KCNQ1...
  75. Choveau F, Shapiro M. Regions of KCNQ K(+) channels controlling functional expression. Front Physiol. 2012;3:397 pubmed publisher
    ..Despite similar structures, KCNQ2 and KCNQ3 homomers yield small current amplitudes compared to other KCNQ homomers and KCNQ2/3 heteromers...
  76. Miceli F, Soldovieri M, Ambrosino P, De Maria M, Migliore M, Migliore R, et al. Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits. J Neurosci. 2015;35:3782-93 pubmed publisher
    Mutations in Kv7.2 (KCNQ2) and Kv7.3 (KCNQ3) genes, encoding for voltage-gated K(+) channel subunits underlying the neuronal M-current, have been associated with a wide spectrum of early-onset epileptic disorders ranging from benign ..
  77. Xu M, Cooper E. An Ankyrin-G N-terminal Gate and Protein Kinase CK2 Dually Regulate Binding of Voltage-gated Sodium and KCNQ2/3 Potassium Channels. J Biol Chem. 2015;290:16619-32 pubmed publisher
    ..Analogous "anchor" peptides within intracellular domains of vertebrate KCNQ2, KCNQ3, and Nav channel α-subunits bind Ankyrin-G (AnkG), thereby mediating concentration of those channels at AISs ..
  78. Strulovich R, Tobelaim W, Attali B, Hirsch J. Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin Complex. Biochemistry. 2016;55:5353-65 pubmed publisher
    ..Functional testing of the chimeric channel found it to have a voltage-dependence similar to the M channel, thereby demonstrating helix A's importance in imparting gating properties. ..
  79. Hirose S, Zenri F, Akiyoshi H, Fukuma G, Iwata H, Inoue T, et al. A novel mutation of KCNQ3 (c.925T-->C) in a Japanese family with benign familial neonatal convulsions. Ann Neurol. 2000;47:822-6 pubmed
    ..a KCNQ potassium channel gene, has been identified as a cause of benign familial neonatal convulsions type 2 (BFNC2). We found a T to C substitution (c...
  80. Afawi Z, Bassan H, Heron S, Oliver K, Straussberg R, Scheffer I, et al. Benign neonatal sleep myoclonus: an autosomal dominant form not allelic to KCNQ2 or KCNQ3. J Child Neurol. 2012;27:1260-3 pubmed
    ..We used microsatellite markers to determine if the disorder was possibly linked to KCNQ2 or KCNQ3, the 2 genes that cause most cases of benign familial neonatal seizures, a disorder that it could be easily ..
  81. Zhang X, Zhang D, Surowy C, Yao B, Jarvis M, McGaraughty S, et al. Development and validation of a medium-throughput electrophysiological assay for KCNQ2/3 channel openers using QPatch HT. Assay Drug Dev Technol. 2013;11:17-24 pubmed publisher
  82. Soldovieri M, Boutry Kryza N, Milh M, Doummar D, Heron B, Bourel E, et al. Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A. Hum Mutat. 2014;35:356-67 pubmed publisher
    Mutations in the KCNQ2 and KCNQ3 genes encoding for Kv 7.2 (KCNQ2; Q2) and Kv 7.3 (KCNQ3; Q3) voltage-dependent K(+) channel subunits, respectively, cause neonatal epilepsies with wide phenotypic heterogeneity...
  83. Dickson E, Jensen J, Hille B. Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P2 and maintenance of KCNQ2/3 ion channel current. Proc Natl Acad Sci U S A. 2014;111:E2281-90 pubmed publisher
  84. Fusco C, Frattini D, Bassi M. A novel KCNQ3 gene mutation in a child with infantile convulsions and partial epilepsy with centrotemporal spikes. Eur J Paediatr Neurol. 2015;19:102-3 pubmed publisher
  85. Kim R, Pless S, Kurata H. PIP2 mediates functional coupling and pharmacology of neuronal KCNQ channels. Proc Natl Acad Sci U S A. 2017;114:E9702-E9711 pubmed publisher
    ..is coupled to changes in voltage sensing, we used voltage-clamp fluorometry to track conformational changes of the KCNQ3 voltage-sensing domains (VSDs) in response to voltage, retigabine, and PIP2...
  86. Selyanko A, Hadley J, Wood I, Abogadie F, Delmas P, Buckley N, et al. Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell. J Neurosci. 1999;19:7742-56 pubmed
    ..It has recently been suggested that the M channel in sympathetic neurons comprises a heteromultimer of KCNQ2 and KCNQ3 (Wang et al., 1998) but it is unclear whether all other M-like currents are generated by these channels...
  87. Cooper E, Aldape K, Abosch A, Barbaro N, Berger M, Peacock W, et al. Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc Natl Acad Sci U S A. 2000;97:4914-9 pubmed
    ..provide information regarding the in vivo distribution and biochemical characteristics of human brain KCNQ2 and KCNQ3, two channel subunits that form M-channels when expressed in vitro, and, when mutated, cause the dominantly ..
  88. Vijai J, Kapoor A, Ravishankar H, Cherian P, Girija A, Rajendran B, et al. Genetic association analysis of KCNQ3 and juvenile myoclonic epilepsy in a South Indian population. Hum Genet. 2003;113:461-3 pubmed
    ..We have tested the association between JME phenotype and an intragenic marker in KCNQ3 by using the transmission disequilibrium test in 119 probands and their parents...
  89. Kanaumi T, Takashima S, Iwasaki H, Itoh M, Mitsudome A, Hirose S. Developmental changes in KCNQ2 and KCNQ3 expression in human brain: possible contribution to the age-dependent etiology of benign familial neonatal convulsions. Brain Dev. 2008;30:362-9 pubmed publisher
    Several mutations of KCNQ2 and KCNQ3 are considered to be associated with benign familial neonatal convulsions (BFNC)...
  90. Stewart A, Gómez Posada J, McGeorge J, Rouhani M, Villarroel A, Murrell Lagnado R, et al. The Kv7.2/Kv7.3 heterotetramer assembles with a random subunit arrangement. J Biol Chem. 2012;287:11870-7 pubmed publisher
    ..Hence, there are no constraints on either the subunit stoichiometry or the subunit arrangement. ..