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Neuronal KCNQ potassium channels:physislogy and role in disease

Nature Reviews Neuroscience volume 1, pages 21–30 (2000)Cite this article

Abstract

Humans have over 70 potassium channel genes, but only some of these have been linked to disease. In this respect, the KCNQ family of potassium channels is exceptional: mutations in four out of five KCNQ genes underlie diseases including cardiac arrhythmias, deafness and epilepsy. These disorders illustrate the different physiological functions of KCNQ channels, and provide a model for the study of the ‘safety margin’ that separates normal from pathological levels of channel expression. In addition, several KCNQ isoforms can associate to form heteromeric channels that underlie the M-current, an important regulator of neuronal excitability.

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Figure 1: The structure of KCNQ channels.
Figure 2: KCNQ2/KCNQ3 heteromers yield currents with the properties of the M-current.
Figure 3: Inhibition of neuronal M-currents leads to hyperexcitability.
Figure 4: Potassium recycling in the scala media of the inner ear.

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References

  1. Bargmann, C. I. Neurobiology of the Caenorhabditis elegans genome. Science 282, 2028–2033 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  2. Lehmann-Horn, F. & Jurkat-Rott, K. Voltage-gated ion channels and hereditary disease. Physiol. Rev. 79, 1317–1372 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Wang, Q. et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nature Genet. 12, 17–23 (1996).

    Article  PubMed  Google Scholar 

  4. Biervert, C. et al. A potassium channel mutation in neonatal human epilepsy. Science 279, 403–406 ( 1998).Full-length KCNQ2 is cloned and shown to be mutated in affected members of a large family with BFNC. The mutation that truncates the C terminus leads to non-functional channels that have no dominant-negative effect on wild-type subunits.

    Article  CAS  PubMed  Google Scholar 

  5. Singh, N. A. et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nature Genet. 18, 25–29 (1998).Positional cloning is used to identify KCNQ2. Several mutations, including a genomic deletion, are found in families with BFNC.

    Article  CAS  PubMed  Google Scholar 

  6. Charlier, C. et al. A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nature Genet. 18, 53–55 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. Neyroud, N. et al. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nature Genet. 15, 186–189 ( 1997).

    Article  CAS  PubMed  Google Scholar 

  8. Kubisch, C. et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 96 , 437–446 (1999). The KCNQ4 channel is cloned by homology. It is mapped to a locus (DFNA2) for dominant deafness, and a mutation in a family with progressive hearing loss is found. It abolishes KCNQ4 currents and exerts a dominant-negative effect. KCNQ4 is localized to outer hair cells by in situ hybridization.

    Article  CAS  PubMed  Google Scholar 

  9. Barhanin, J. et al. KvLQT1 and IsK (minK) proteins associate to form the I Ks cardiac potassium current. Nature 384, 78–80 (1996). In parallel to the work by Sanguinetti et al . this paper finally identifies KCNQ1 as the partner for KCNE1 (minK, IsK).

    Article  CAS  PubMed  Google Scholar 

  10. Sanguinetti, M. C. et al. Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKs potassium channel. Nature 384, 80–83 (1996). In parallel to the work by Barhanin et al . this paper shows that KCNQ1 and KCNE1 underlie the I Ks current. It also shows that oocytes express a KCNQ1 homologue, which explains why Xenopus oocytes were the only expression system in which KCNE1 could be expressed previously.

    Article  CAS  PubMed  Google Scholar 

  11. Vetter, D. E. et al. Inner ear defects induced by null mutation of the isk gene. Neuron 17, 1251–1264 (1996).The first disruption of the Kcne1 (isk ) gene in mice. This thorough study shows a collapse of the scala media shortly after birth. Transepithelial measurements show that the current across the stria vascularis is nearly abolished.

    Article  CAS  PubMed  Google Scholar 

  12. Schroeder, B. C. et al. A constitutively open potassium channel formed by KCNQ1 and KCNE3. Nature 403, 196– 199 (2000).KCNE3 is shown to greatly affect KCNQ1 gating. It acts differently from KCNE1 by constitutively opening the channel. In situ hybridization and comparison with native currents indicate that the KCNQ1/ KCNE3 channel may be important for intestinal chloride secretion.

    Article  CAS  PubMed  Google Scholar 

  13. Wang, H. S. et al. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 282, 1890– 1893 (1998).The kinetic and pharmacological properties of KCNQ2/KCNQ3 heteromeric channels are shown to correlate with those of M-currents. This work finally indicates a solution to the molecular identity of this important regulator of neuronal excitability.

    Article  CAS  PubMed  Google Scholar 

  14. Brown, D. A. & Adams, P. R. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature 283, 673–676 ( 1980).

    Article  CAS  PubMed  Google Scholar 

  15. Schroeder, B. C., Kubisch, C., Stein, V. & Jentsch, T. J. Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature 396, 687– 690 (1998).Like reference 13, this work shows that KCNQ2 and KCNQ3 form heteromers. Analysis of KCNQ2 and KCNQ3 mutants within this heteromer indicates that the loss of currents in heterozygous patients with BFNC is surprisingly small (25%). In addition, KCNQ2/KCNQ3 currents are shown to be activated by cAMP.

    Article  CAS  PubMed  Google Scholar 

  16. Watanabe, H. et al. Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability . J. Neurochem. 75, 28– 33 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Schroeder, B. C., Hechenberger, M., Weinreich, F., Kubisch, C. & Jentsch, T. J. KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents. J. Biol. Chem. 275, 24089–24095 ( 2000).Identification of KCNQ5, which is shown to be broadly expressed in brain and sympathetic ganglia. It can form heteromers with KCNQ3 and can be inhibited by muscarinic stimulation. The cloning and characterization of KCNQ5 is also reported in reference 18.

    Article  CAS  PubMed  Google Scholar 

  18. Lerche, C. et al. Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M-current diversity. J. Biol. Chem. 275, 22395–22400 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Kharkovets, T. et al. KCNQ4, a K+-channel mutated in a form of dominant deafness, is expressed in the inner ear and in the central auditory pathway . Proc. Natl Acad. Sci. USA 97, 4333– 4338 (2000).KCNQ4 antibodies are used to show that, in the inner ear, KCNQ4 is expressed primarily in outer hair cells of the cochlea and in type I hair cells of the vestibular organ. Confirming previous speculation that it may mediate potassium efflux, its expression in outer hair cells is restricted to the basal membrane. Surprisingly, KCNQ4 is also expressed in neurons on the central auditory pathway of the brainstem.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kirsch, G. E. Ion channel defects in cardiac arrhythmia. J. Membr. Biol. 170, 181–190 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Viskin, S. Long QT syndromes and torsade de pointes. Lancet 354 , 1625–1633 (1999).

    Article  CAS  PubMed  Google Scholar 

  22. Schulze-Bahr, E. et al. The LQT syndromes–current status of molecular mechanisms . Z. Kardiol. 88, 245–254 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. Nerbonne, J. M. Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium. J. Physiol. (Lond.) 525, 285 –298 (2000).

    Article  CAS  Google Scholar 

  24. Schwake, M., Pusch, M., Kharkovets, T. & Jentsch, T. J. Surface expression and single-channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. J. Biol. Chem. 275, 13343–13348 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Schmitt, N. et al. A recessive C-terminal Jervell and Lange-Nielsen mutation of the KCNQ1 channel impairs subunit assembly. EMBO J. 19, 332–340 (2000). A C-terminal domain of KCNQ1 is suggested to be important for subunit interactions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tinel, N., Lauritzen, I., Chouabe, C., Lazdunski, M. & Borsotto, M. The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3. FEBS Lett. 438, 171 –176 (1998).

    Article  CAS  PubMed  Google Scholar 

  27. Yang, W. P. et al. Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. J. Biol. Chem. 273, 19419–19423 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  28. Cooper, E. C. et al. Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc. Natl Acad. Sci. USA 97, 4914–4919 ( 2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nakamura, M. et al. KQT2, a new putative potassium channel family produced by alternative splicing. Isolation, genomic structure, and alternative splicing of the putative potassium channels. Receptors Channels 5, 255–271 (1998).

    CAS  PubMed  Google Scholar 

  30. Hadley, J. K. et al. Differential tetraethylammonium sensitivity of KCNQ1-4 potassium channels. Br. J. Pharmacol. 129, 413– 415 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yang, W. P. et al. KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias. Proc. Natl Acad. Sci. USA 94, 4017–4021 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gardiner, M. & Lehesjoki, A. E. Genetics of the epilepsies . Curr. Opin. Neurol. 13, 157– 164 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. Steinlein, O. K. & Noebels, J. L. Ion channels and epilepsy in man and mouse. Curr. Opin. Genet. Dev. 10, 286–291 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Ronen, G. M., Rosales, T. O., Connolly, M., Anderson, V. E. & Leppert, M. Seizure characteristics in chromosome 20 benign familial neonatal convulsions. Neurology 43, 1355–1360 (1993).

    Article  CAS  PubMed  Google Scholar 

  35. Leppert, M. et al. Benign familial neonatal convulsions linked to genetic markers on chromosome 20. Nature 337, 647– 648 (1989).

    Article  CAS  PubMed  Google Scholar 

  36. Lewis, T. B., Leach, R. J., Ward, K., O'Connell, P. & Ryan, S. G. Genetic heterogeneity in benign familial neonatal convulsions: identification of a new locus on chromosome 8q. Am. J. Hum. Genet. 53, 670–675 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lerche, H. et al. A reduced K+ current due to a novel mutation in KCNQ2 causes neonatal convulsions. Ann. Neurol. 46, 305–312 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Biervert, C. & Steinlein, O. K. Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions. Hum. Genet. 104, 234–240 (1999).

    CAS  PubMed  Google Scholar 

  39. Lee, W. L. et al. A KCNQ2 splice site mutation causing benign neonatal convulsions in a Scottish family. Neuropediatrics 31, 9–12 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Hirose, S. et al. A novel mutation of KCNQ3 (c.925T→C) in a Japanese family with benign familial neonatal convulsions. Ann. Neurol. 47, 822–826 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Steinlein, O. K., Stoodt, J., Biervert, C., Janz, D. & Sander, T. The voltage gated potassium channel KCNQ2 and idiopathic generalized epilepsy. Neuroreport 10, 1163 –1166 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Marrion, N. V. Control of M-current. Annu. Rev. Physiol. 59, 483–504 (1997).

    Article  CAS  PubMed  Google Scholar 

  43. Lamas, J. A., Selyanko, A. A. & Brown, D. A. Effects of a cognition-enhancer, linopirdine (DuP 996), on M-type potassium currents (IK(M)) and some other voltage- and ligand-gated membrane currents in rat sympathetic neurons. Eur. J. Neurosci. 9, 605–616 (1997).

    Article  CAS  PubMed  Google Scholar 

  44. Shapiro, M. S. et al. Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K+ channels that underlie the neuronal M current. J. Neurosci. 20, 1710–1721 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Selyanko, A. A. et al. Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic receptors. J. Physiol. (Lond.) 522, 349–355 (2000).

    Article  CAS  Google Scholar 

  46. Sims, S. M., Singer, J. J. & Walsh, J. V. Jr Antagonistic adrenergic-muscarinic regulation of M current in smooth muscle cells. Science 239, 190–193 (1988).

    Article  CAS  PubMed  Google Scholar 

  47. Zaczek, R. et al. Two new potent neurotransmitter release enhancers, 10,10-bis(4- pyridinylmethyl)-9(10H)-anthracenone and 10,10-bis(2-fluoro-4- pyridinylmethyl)-9(10H)-anthracenone: comparison to linopirdine. J. Pharmacol. Exp. Ther. 285, 724–730 (1998).

    CAS  PubMed  Google Scholar 

  48. Rundfeldt, C. & Netzer, R. The novel anticonvulsant retigabine activates M-currents in chinese hamster ovary-cells transfected with human KCNQ2/3 subunits. Neurosci. Lett. 282, 73 –76 (2000).

    Article  CAS  PubMed  Google Scholar 

  49. Selyanko, A. A. et al. Two types of K+ channel subunits, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell. J. Neurosci. 19, 7742–7756 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Meves, H., Schwarz, J. R. & Wulfsen, I. Separation of M-like current and ERG current in NG108-15 cells. Br. J. Pharmacol. 127, 1213– 1223 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kananura, C., Biervert, C., Hechenberger, M., Engels, H. & Steinlein, O. K. The new voltage gated potassium channel KCNQ5 and neonatal convulsions. Neuroreport 11, 2063–2067 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Coucke, P. et al. Linkage of autosomal dominant hearing loss to the short arm of chromosome 1 in two families. N. Engl. J. Med. 331 , 425–431 (1994).

    Article  CAS  PubMed  Google Scholar 

  53. Coucke, P. J. et al. Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families. Hum. Mol. Genet. 8, 1321–1328 (1999).

    Article  CAS  PubMed  Google Scholar 

  54. Sakagami, M. et al. Cellular localization of rat Isk protein in the stria vascularis by immunohistochemical observation. Hear. Res. 56, 168–172 (1991).

    Article  CAS  PubMed  Google Scholar 

  55. Schulze-Bahr, E. et al. KCNE1 mutations cause Jervell and Lange-Nielsen syndrome. Nature Genet. 17, 267–268 (1997).

    Article  CAS  PubMed  Google Scholar 

  56. Delpire, E., Lu, J., England, R., Dull, C. & Thorne, T. Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter. Nature Genet. 22, 192–195 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Ryan, A. & Dallos, P. Effect of absence of cochlear outer hair cells on behavioural auditory threshold. Nature 253, 44–46 (1975).

    Article  CAS  PubMed  Google Scholar 

  58. Kelsell, D. P. et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 387, 80– 83 (1997).

    Article  CAS  PubMed  Google Scholar 

  59. Grifa, A. et al. Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nature Genet. 23, 16– 18 (1999).

    Article  CAS  PubMed  Google Scholar 

  60. Xia, J. H. et al. Mutations in the gene encoding gap junction protein β-3 associated with autosomal dominant hearing impairment. Nature Genet. 20, 370–373 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  61. Stojkovic, T., Latour, P., Vandenberghe, A., Hurtevent, J. F. & Vermersch, P. Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q). Neurology 52, 1010–1014 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Kikuchi, T., Kimura, R. S., Paul, D. L. & Adams, J. C. Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anat. Embryol. (Berl.) 191, 101 –118 (1995).

    Article  CAS  Google Scholar 

  63. Lautermann, J. et al. Expression of the gap-junction connexins 26 and 30 in the rat cochlea. Cell Tissue Res. 294, 415– 420 (1998).

    Article  CAS  PubMed  Google Scholar 

  64. Nakagawa, T. et al. Ionic properties of IK,n in outer hair cells of guinea pig cochlea. Brain Res. 661, 293 –297 (1994).

    Article  CAS  PubMed  Google Scholar 

  65. Santos-Sacchi, J., Huang, G. J. & Wu, M. Mapping the distribution of outer hair cell voltage-dependent conductances by electrical amputation. Biophys. J. 73, 1424–1429 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Marcotti, W. & Kros, C. J. Developmental expression of the potassium current IK,n contributes to maturation of mouse outer hair cells. J. Physiol. (Lond.) 520, 653–660 (1999).

    Article  CAS  Google Scholar 

  67. Chen, J. W. & Eatock, R. A. Major potassium conductance in type I hair cells from rat semicircular canals: characterization and modulation by nitric oxide. J. Neurophysiol. 84, 139 –151 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Trussell, L. O. Synaptic mechanisms for coding timing in auditory neurons. Annu. Rev. Physiol. 61, 477–496 (1999).

    Article  CAS  PubMed  Google Scholar 

  69. Priori, S. G. et al. A recessive variant of the Romano-Ward long-QT syndrome? Circulation 97, 2420–2425 (1998).

    Article  CAS  PubMed  Google Scholar 

  70. Larsen, L. A. et al. Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene. Eur. J. Hum. Genet. 7, 724–728 (1999).

    Article  CAS  PubMed  Google Scholar 

  71. Chouabe, C. et al. Novel mutations in KvLQT1 that affect IKs activation through interactions with Isk. Cardiovasc. Res. 45, 971–980 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Coucke, P. J. et al. Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families. Hum. Mol. Genet. 8, 1321–1328 (1999).

    Article  CAS  PubMed  Google Scholar 

  73. Talebizadeh, Z., Kelley, P. M., Askew, J. W., Beisel, K. W. & Smith, S. D. Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss. Hum. Mutat. 14, 493–501 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  74. Chouabe, C. et al. Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J. 16, 5472–5479 ( 1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Russell, M. W., Dick, M., Collins, F. S. & Brody, L. C. KVLQT1 mutations in three families with familial or sporadic long QT syndrome. Hum. Mol. Genet. 5, 1319–1324 (1996).

    Article  CAS  PubMed  Google Scholar 

  76. Wollnik, B. et al. Pathophysiological mechanisms of dominant and recessive KvLQT1 K+ channel mutations found in inherited cardiac arrhythmias . Hum. Mol. Genet. 6, 1943– 1949 (1997).

    Article  CAS  PubMed  Google Scholar 

  77. Robbins, J., Marsh, S. J. & Brown, D. A. On the mechanism of M-current inhibition by muscarinic m1 receptors in DNA-transfected rodent neuroblastoma x glioma cells. J. Physiol. (Lond.) 469, 153–178 (1993).

    Article  CAS  Google Scholar 

  78. Offner, F. F., Dallos, P. & Cheatham, M. A. Positive endocochlear potential: mechanism of production by marginal cells of stria vascularis. Hear. Res. 29 , 117–124 (1987).

    Article  CAS  PubMed  Google Scholar 

  79. Wangemann, P., Liu, J. & Marcus, D. C. Ion transport mechanisms responsible for K+ secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro. Hear. Res. 84, 19– 29 (1995).

    Article  CAS  PubMed  Google Scholar 

  80. Tyson, J. et al. IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome. Hum. Mol. Genet. 6, 2179–2185 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. Dixon, M. J. et al. Mutation of the Na-K-Cl co-transporter gene Slc12a2 results in deafness in mice. Hum. Mol. Genet. 8, 1579–1584 (1999).

    Article  CAS  PubMed  Google Scholar 

  82. Flagella, M. et al. Mice lacking the basolateral Na-K-2Cl cotransporter have impaired epithelial chloride secretion and are profoundly deaf. J. Biol. Chem. 274, 26946–28955 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  83. Pickles, J. O. & Corey, D. P. Mechanoelectrical transduction by hair cells. Trends Neurosci. 15, 254–259 (1992).

    Article  CAS  PubMed  Google Scholar 

  84. Zheng, J. et al. Prestin is the motor protein of cochlear outer hair cells. Nature 405, 149–155 ( 2000).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Work in my laboratory is supported by the Deutsche Forschungsgemeinschaft, the European Community, the Fonds der Chemischen Industrie and the Louis-Jeantet Prize for Medicine.

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Authors and Affiliations

  1. Zentrum für Molekulare Neurobiologie Hamburg, ZMNH, Hamburg University, Martinistrasse 85, Hamburg, D-20246, Germany

    Thomas J. Jentsch

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DATABASE LINKS

KCNQ1

LQTS

JLNS

KCNE1

KCNE3

KCNQ2

KCNQ3

BFNC

KCNQ5

KCNQ4

DFNA2

connexin 26

connexin 30

connexin 31

connexin 32

FURTHER INFORMATION

Potassium channel nomenclature

Thomas Jentsch's laboratory

ENCYCLOPEDIA OF LIFE SCIENCES

Hair cells

Glossary

SPLICE VARIANTS

Further forms of a protein derived from alternative processing of its mRNA.

HETEROMERS

Channels formed by the assembly of two or more different subunits.

HOMOMERIC CHANNELS

Channels formed by several copies of a single subunit.

POSITIONAL CLONING

A strategy for identifying a gene associated with a genetic disease in which the phenotype is correlated with a chromosomal site and the DNA cloned and compared with that in normal individuals.

DOMINANT NEGATIVE

A mutant protein that interacts with the normal form and blocks its function.

NOISE ANALYSIS

A technique in which the random fluctuations in membrane potential are used to give information on the properties of single channels.

MISSENSE MUTATION

A mutation in which an incorrect amino acid is incorporated into the protein.

FRAME-SHIFT MUTATION

The addition or deletion of a nucleotide such that the protein sequence from that point onwards is altered.

SPLICE-SITE MUTATION

A mutation at the site where the mRNA is processed to generate protein variants.

HAPLOINSUFFICIENCY

Loss of one copy (one allele) of a gene is sufficient to give rise to disease. Haploinsufficiency implies that no dominant-negative effect of the mutated gene product has to be invoked.

POLYGENIC

A characteristic controlled by different genes, each of which have only a small role in the phenotype.

STRIA VASCULARIS

The lateral part of the scala media, which contains the epithelia that secrete the endolymph.

ORGAN OF CORTI

The primary sensory organ of hearing. It is located on the floor of the scala media, and consists of sensory hair cells (one row of inner hair cells and three rows of outer hair cells) and supporting cells. The stereocilia of the hair cells touch the gelatinous tectorial membrane, which covers the organ.

ENDOLYMPH

The fluid filling the scala media of the cochlea and the cavities of the vestibular organ. In contrast to the perilymph, which fills the scala tympani and scala vestibuli, it has an unusual ion composition with a high potassium concentration.

SCALA MEDIA

The central cavity of the cochlea that is sandwiched between the scala vestibuli (which receives acoustic input through the ossicles of the middle ear) and the scala tympani. It is filled with endolymph and contains the organ of Corti.

GAP JUNCTIONS

Channels that connect adjacent cells and allow for the free passage of small molecules. They are formed by proteins called connexins.

GENE DOSAGE

The number of times a gene appears in the genome.

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Jentsch, T. Neuronal KCNQ potassium channels:physislogy and role in disease. Nat Rev Neurosci 1, 21–30 (2000). https://doi.org/10.1038/35036198

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