KCNQ4 explained

Potassium voltage-gated channel subfamily KQT member 4, also known as voltage-gated potassium channel subunit K_v7.4, is a protein that in humans is encoded by the KCNQ4 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene.

Clinical significance

The current generated by this channel is inhibited by muscarinic acetylcholine receptor M1 and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene.

Ligands

• ML213: KCNQ2/Q4 channel opener.^[4]

See also

• Voltage-gated potassium channel

Further reading

• Coucke PJ, Van Hauwe P, Kelley PM, etal . Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families . Hum. Mol. Genet. . 8 . 7 . 1321–8 . 1999 . 10369879 . 10.1093/hmg/8.7.1321 . free .
• Talebizadeh Z, Kelley PM, Askew JW, etal . Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss . Hum. Mutat. . 14 . 6 . 493–501 . 2000 . 10571947 . 10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P . 13288075 . free .
• Selyanko AA, Hadley JK, Wood IC, etal . Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors . J. Physiol. . 522 . 3. 349–55 . 2000 . 10713961 . 10.1111/j.1469-7793.2000.t01-2-00349.x . 2269765 .
• Van Hauwe P, Coucke PJ, Ensink RJ, etal . Mutations in the KCNQ4 K+ channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region . Am. J. Med. Genet. . 93 . 3 . 184–7 . 2000 . 10925378 . 10.1002/1096-8628(20000731)93:3<184::AID-AJMG4>3.0.CO;2-5 .
• Beisel KW, Nelson NC, Delimont DC, Fritzsch B . Longitudinal gradients of KCNQ4 expression in spiral ganglion and cochlear hair cells correlate with progressive hearing loss in DFNA2 . Brain Res. Mol. Brain Res. . 82 . 1–2 . 137–49 . 2001 . 11042367 . 10.1016/S0169-328X(00)00204-7 .
• Søgaard R, Ljungstrøm T, Pedersen KA, etal . KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology . Am. J. Physiol., Cell Physiol. . 280 . 4 . C859–66 . 2001 . 11245603 . 10.1152/ajpcell.2001.280.4.C859. 7891527 .
• Van Camp G, Coucke PJ, Akita J, etal . A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment . Hum. Mutat. . 20 . 1 . 15–9 . 2002 . 12112653 . 10.1002/humu.10096 . 22495155 . free .
• Stern RE, Lalwani AK . Audiologic evidence for further genetic heterogeneity at DFNA2 . Acta Otolaryngol. . 122 . 7 . 730–5 . 2003 . 12484650 . 10.1080/003655402/000028059 .
• Schwake M, Jentsch TJ, Friedrich T . A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly . EMBO Rep. . 4 . 1 . 76–81 . 2003 . 12524525 . 10.1038/sj.embor.embor715 . 1315815 .
• Li Y, Langlais P, Gamper N, etal . Dual phosphorylations underlie modulation of unitary KCNQ K(+) channels by Src tyrosine kinase . J. Biol. Chem. . 279 . 44 . 45399–407 . 2004 . 15304482 . 10.1074/jbc.M408410200 . free .
• Chambard JM, Ashmore JF . Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway . Pflügers Arch. . 450 . 1 . 34–44 . 2005 . 15660259 . 10.1007/s00424-004-1366-2 . 21570482 .
• Van Laer L, Carlsson PI, Ottschytsch N, etal . The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss . Hum. Mutat. . 27 . 8 . 786–95 . 2006 . 16823764 . 10.1002/humu.20360 . 25357017 .
• Van Eyken E, Van Laer L, Fransen E, etal . KCNQ4: a gene for age-related hearing impairment? . Hum. Mutat. . 27 . 10 . 1007–16 . 2006 . 16917933 . 10.1002/humu.20375 . 8912727 .
• Su CC, Yang JJ, Shieh JC, etal . Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic deafness from Taiwan . Audiol. Neurootol. . 12 . 1 . 20–6 . 2007 . 17033161 . 10.1159/000096154 . 25256223 .
• Jensen HS, Grunnet M, Olesen SP . Inactivation as a New Regulatory Mechanism for Neuronal Kv7 Channels . Biophys. J. . 92 . 8 . 2747–56 . 2007 . 17237198 . 10.1529/biophysj.106.101287 . 1831682 . 2007BpJ....92.2747J .
• Howard RJ, Clark KA, Holton JM, Minor DL . Structural Insight into KCNQ (Kv7) Channel Assembly and Channelopathy . Neuron . 53 . 5 . 663–75 . 2007 . 17329207 . 10.1016/j.neuron.2007.02.010 . 3011230 .
• Iannotti FA, Panza E, Barrese V, Viggiano D, Soldovieri MV, Taglialatela M . Expression, localization, and pharmacological role of Kv7 potassium channels in skeletal muscle proliferation, differentiation, and survival after myotoxic insults . J. Pharmacol. Exp. Ther. . 332 . 3 . 811–20 . March 2010 . 20040580 . 10.1124/jpet.109.162800 . 17248733 .
• Iannotti FA, Barrese V, Formisano L, Taglialatela M . Specification of skeletal muscle differentiation by repressor element-1 silencing transcription factor (REST)-regulated Kv7.4 potassium channels.. Mol Biol Cell. 24 . 3 . 274–84. Feb 2013 . 23242999 . 10.1091/mbc.E11-12-1044 . 3564528.

External links

• GeneReviews/NCBI/NIH/UW entry on Deafness and Hereditary Hearing Loss Overview
  • GeneReviews/NCBI/NIH/UW entry on DFNA2 Nonsyndromic Hearing Loss

Notes and References

1. Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch TJ . KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness . Cell . 96 . 3 . 437–46 . Mar 1999 . 10025409 . 10.1016/S0092-8674(00)80556-5 . free .
2. Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X . International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels . Pharmacol Rev . 57 . 4 . 473–508 . Dec 2005 . 16382104 . 10.1124/pr.57.4.10 . 219195192 .
3. Web site: Entrez Gene: KCNQ4 potassium voltage-gated channel, KQT-like subfamily, member 4.
4. Yu H, Wu M, Townsend SD, etal . Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener . ACS Chem Neurosci . 2 . 10 . 572–577 . 2011 . 22125664 . 3223964 . 10.1021/cn200065b .