Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits

Journal of Neuroscience

Volumn 35, Issue 9, 2015, Pages 3782-3793

  Miceli, Francesco ^a   Soldovieri, Maria Virginia ^b   Ambrosino, Paolo ^b   De Maria, Michela ^b   Migliore, Michele ^c   Migliore, Rosanna ^c   Taglialatela, Maurizio ^a,b  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b UNIVERSITY OF MOLISE   (Italy)

^c CNR   (Italy)

Author keywords

Epileptic encephalopathies; Gating; Kv7 potassium channels; Mutations; Voltage sensing domain

Indexed keywords

UNCLASSIFIED DRUG; VOLTAGE GATED POTASSIUM CHANNEL; VOLTAGE GATED POTASSIUM CHANNEL KV7.2; VOLTAGE GATED POTASSIUM CHANNEL KV7.3; COMPLEMENTARY DNA; POTASSIUM CHANNEL KCNQ2; POTASSIUM CHANNEL KCNQ3;

ANIMAL CELL; ARTICLE; BIOTINYLATION; CHEMOLUMINESCENCE; CONTROLLED STUDY; EARLY ONSET EPILEPTIC ENCEPHALOPATHY; EPILEPSY; FEMALE; GAIN OF FUNCTION MUTATION; LOSS OF FUNCTION MUTATION; MEMBRANE DEPOLARIZATION; MUTAGENESIS; NERVE CELL EXCITABILITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; SENSITIVITY ANALYSIS; STATIC ELECTRICITY; STRUCTURE ANALYSIS; WESTERN BLOTTING; AMINO ACID SEQUENCE; ANIMAL; BENIGN CHILDHOOD EPILEPSY; BIOSYNTHESIS; CHEMICAL STRUCTURE; CHO CELL LINE; CRICETULUS; GENETICS; HAMSTER; HUMAN; MOLECULAR GENETICS; MUTATION; PATHOPHYSIOLOGY; PROTEIN TERTIARY STRUCTURE;

AMINO ACID SEQUENCE; ANIMALS; BIOTINYLATION; CHO CELLS; CRICETINAE; CRICETULUS; DNA, COMPLEMENTARY; EPILEPSY, BENIGN NEONATAL; HUMANS; KCNQ2 POTASSIUM CHANNEL; KCNQ3 POTASSIUM CHANNEL; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; PROTEIN STRUCTURE, TERTIARY;

EID: 84924787957     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4423-14.2015     Document Type: Article

References (73)

1. Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, et al. (2013) De novo mutations in epileptic encephalopathies. Nature 501:217–221.
2. Ascoli GA, Gasparini S, Medinilla V, Migliore M (2010) Local control of postinhibitory rebound spiking in CA1 pyramidal neuron dendrites. J Neurosci 30:6434–6442.
3. Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R (2012) De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet 44:1255–1259.
4. Battefeld A, Tran BT, Gavrilis J, Cooper EC, Kole MH (2014) Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons. J Neurosci 34:3719–3732.
5. Bertrand S, Lacaille JC (2001) Unitary synaptic currents between lacunosum-moleculare interneurones and pyramidal cells in rat hippocampus. J Physiol 532:369–384.
6. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK (1998) A potassium channel mutation in neonatal human epilepsy. Science 279:403–406.
7. Borgatti R, Zucca C, Cavallini A, Ferrario M, Panzeri C, Castaldo P, Soldovieri MV, Baschirotto C, Bresolin N, Dalla Bernardina B, Taglialatela M, Bassi MT (2004) A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology 63:57–65.
8. Careaga CL, Falke JJ (1992) Thermal motions of surface alpha-helices in the D-galactose chemosensory receptor: detection by disulfide trapping. J Mol Biol 226:1219–1235.
9. Carvill GL, Heavin SB, Yendle SC, McMahon JM, O’Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, et al. (2013) Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genet 45:825–830.
10. Castaldo P, del Giudice EM, Coppola G, Pascotto A, Annunziato L, Taglialatela M (2002) Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3 potassium channels. J Neurosci 22:RC199.
11. Castaldo P, Stefanoni P, Miceli F, Coppola G, Del Giudice EM, Bellini G, Pascotto A, Trudell JR, Harrison NL, Annunziato L, Taglialatela M (2004) A novel hyperekplexia-causing mutation in the pre-transmembrane segment 1 of the human glycine receptor alpha1 subunit reduces membrane expression and impairs gating by agonists. J Biol Chem 279:25598–25604.
12. Catterall WA, Kalume F, Oakley JC (2010) NaV1.1 channels and epilepsy. J Physiol 588:1849–1859.
13. Cavaretta JP, Sherer KR, Lee KY, Kim EH, Issema RS, Chung HJ (2014) Polarized axonal surface expression of neuronal KCNQ potassium channels is regulated by calmodulin interaction with KCNQ2 subunit. PLoS One 9:e103655.
14. Charlier C, Singh NA, Ryan SG, Lewis TB, Reus BE, Leach RJ, Leppert M (1998) A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet 18:53–55.
15. Chung HJ, Jan YN, Jan LY (2006) 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 USA 103:8870-8875.
16. Cross JH, Guerrini R (2013) The epileptic encephalopathies. Handb Clin Neurol 111:619–626.
17. 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 USA 98:12272-12277.
18. Devaux JJ, Kleopa KA, Cooper EC, Scherer SS (2004) KCNQ2 is a nodal K + channel. J Neurosci 24:1236–1244.
19. Du W, Bautista JF, Yang H, Diez-Sampedro A, You SA, Wang L, Kotagal P, Lu¨ders HO, Shi J, Cui J, Richerson GB, Wang QK (2005) Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet 37:733–738.
20. Foster TC, Dumas TC (2001) Mechanism for increased hippocampal synaptic strength following differential experience. J Neurophysiol 85:1377-1383.
21. Harty RC, Kim TH, Thomas EA, Cardamone L, Jones NC, Petrou S, Wimmer VC (2013) Axon initial segment structural plasticity in animal models of genetic and acquired epilepsy. Epilepsy Res 105:272–279.
22. Hines ML, Carnevale NT (1997) The NEURON simulation environment. Neural Comput 9:1179–1209.
23. Hu H, Vervaeke K, Storm JF (2002) Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na current in rat hippocampal pyramidal cells. J Physiol 545:783–805.
24. Hu H, Vervaeke K, Storm JF (2007) M-channels (Kv7/KCNQ channels) that regulate synaptic integration, excitability, and spike pattern of CA1 pyramidal cells are located in the perisomatic region. J Neurosci 27:1853-1867.
25. Hu H, Vervaeke K, Graham LJ, Storm JF (2009) Complementary theta resonance filtering by two spatially segregated mechanisms in CA1 hippocampal pyramidal neurons. J Neurosci 29:14472–14483.
26. Jensen MØ, Jogini V, Borhani DW, Leffler AE, Dror RO, Shaw DE (2012) Mechanism of voltage gating in potassium channels. Science 336:229-233.
27. Jentsch TJ (2000) Neuronal KCNQ potassium channels: physiology and role in disease. Nat Rev Neurosci 1:21–30.
28. Kato M, Yamagata T, Kubota M, Arai H, Yamashita S, Nakagawa T, Fujii T, Sugai K, Imai K, Uster T, Chitayat D, Weiss S, Kashii H, Kusano R, Matsumoto A, Nakamura K, Oyazato Y, Maeno M, Nishiyama K, Kodera H, et al. (2013) Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia 54:1282–1287.
29. Kofuji P, Hofer M, Millen KJ, Millonig JH, Davidson N, Lester HA, Hatten ME (1996) Functional analysis of the weaver mutant GIRK2 K + channel and rescue of weaver granule cells. Neuron 16:941–952.
30. Kole MH, Cooper EC (2014) Axonal Kv7.2/7.3 channels: caught in the act. Channels 8:288–289.
31. Lamsa K, Irvine EE, Giese KP, Kullmann DM (2007) NMDA receptor-dependent long-term potentiation in mouse hippocampal interneurons shows a unique dependence on Ca +/calmodulin-dependent kinases. J Physiol 584:885–894.
32. Lawrence JJ, Saraga F, Churchill JF, Statland JM, Travis KE, Skinner FK, McBain CJ (2006) Somatodendritic Kv7/KCNQ/M channels control in-terspike interval in hippocampal interneurons. J Neurosci 26:12325-12338.
33. Lee H, Lin MC, Kornblum HI, Papazian DM, Nelson SF (2014) Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation. Hum Mol Genet 23:3481–3489.
34. Liu W, Devaux JJ (2014) Calmodulin orchestrates the heteromeric assembly and the trafficking of KCNQ2/3 (Kv7.2/3) channels in neurons. Mol Cell Neurosci 58:40–52.
35. Long SB, Tao X, Campbell EB, MacKinnon R (2007) Atomic structure of a voltage-dependent K + channel in a lipid membrane-like environment. Nature 450:376–382.
36. Marcelin B, Chauviere L, Becker A, Migliore M, Esclapez M, Bernard C (2009) H channel-dependent deficit of theta oscillation resonance and phase shift in temporal lobe epilepsy. Neurobiol Dis 33:436–447.
37. 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 24:592–597.
38. Miceli F, Soldovieri MV, Hernandez CC, Shapiro MS, Annunziato L, Taglialatela M (2008) Gating consequences of charge neutralization of argi-nine residues in the S4 segment of K(v)7.2, an epilepsy-linked K + channel subunit. Biophys J 95:2254–2264.
39. Miceli F, Vargas E, Bezanilla F, Taglialatela M (2012) Gating currents from Kv7 channels carrying neuronal hyperexcitability mutations in the voltage-sensing domain. Biophys J 102:1372–1382.
40. Miceli F, Soldovieri MV, Ambrosino P, Barrese V, Migliore M, Cilio MR, Taglialatela M (2013) Genotype-phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of K(v)7.2 potassium channel subunits. Proc Natl Acad Sci USA 110:4386–4391.
41. Migliore M (2003) On the integration of subthreshold inputs from per-forant path and Schaffer collaterals in hippocampal CA1 pyramidal neurons. J Comput Neurosci 14:185–192.
42. Migliore M, Ferrante M, Ascoli GA (2005) Signal propagation in oblique dendrites of CA1 pyramidal cells. JNeurophysiol94:4145– 4155.
43. Milligan CJ, Li M, Gazina EV, Heron SE, Nair U, Trager C, Reid CA, Venkat A, Younkin DP, Dlugos DJ, Petrovski S, Goldstein DB, Dibbens LM, Scheffer IE, Berkovic SF, Petrou S (2014) KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine. Ann Neurol 75:581–590.
44. Minneci F, Janahmadi M, Migliore M, Dragicevic N, Avossa D, Cherubini E (2007) Signaling properties of stratum oriens interneurons in the hippocampus of transgenic mice expressing EGFP in a subset of somatostatin-containing cells. Hippocampus 17:538–553.
45. Nava C, Dalle C, Rastetter A, Striano P, de Kovel CG, Nabbout R, Cances C, Ville D, Brilstra EH, Gobbi G, Raffo E, Bouteiller D, Marie Y, Trouillard O, Robbiano A, Keren B, Agher D, Roze E, Lesage S, Nicolas A, et al. (2014) De novo mutations in HCN1 cause early infantile epileptic encephalopathy. Nat Genet 46:640–645.
46. Nigro MJ, Mateos-Aparicio P, Storm JF (2014) Expression and functional roles of Kv7/KCNQ/M-channels in rat medial entorhinal cortex layer II stellate cells. J Neurosci 34:6807–6812.
47. Novarino G, Baek ST, Gleeson JG (2013) The sacred disease: the puzzling genetics of epileptic disorders. Neuron 80:9–11.
48. Orhan G, Bock M, Schepers D, Ilina EI, Reichel SN, Löffler H, Jezutkovic N, Weckhuysen S, Mandelstam S, Suls A, Danker T, Guenther E, Scheffer IE, De Jonghe P, Lerche H, Maljevic S (2014) Dominant-negative effects of KCNQ2 mutations are associated with epileptic encephalopathy. Ann Neurol 75:382–394.
49. Panaghie G, Abbott GW (2007) The role of S4 charges in voltage-dependent and voltage-independent KCNQ1 potassium channel complexes. J Gen Physiol 129:121–133.
50. Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Ropke A, Moog U, Riess A, Thiel CT, et al. (2012) Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability an exome sequencing study. Lancet 380:1674–1682.
51. Robinson RB, Siegelbaum SA (2003) Hyperpolarization-activated cation currents: from molecules to physiological function. Annu Rev Physiol 65:453–480.
52. Rossi P, De Filippi G, Armano S, Taglietti V, D’Angelo E (1998) The weaver mutation causes a loss of inward rectifier current regulation in premigratory granule cells of the mouse cerebellum. J Neurosci 18:3537–3547.
53. Saitsu H, Kato M, Koide A, Goto T, Fujita T, Nishiyama K, Tsurusaki Y, Doi H, Miyake N, Hayasaka K, Matsumoto N (2012) Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome. Ann Neurol 72:298–300.
54. Schwarz JR, Glassmeier G, Cooper EC, Kao TC, Nodera H, Tabuena D, Kaji R, Bostock H (2006) KCNQ channels mediate IKs, a slow K + current regulating excitability in the rat node of Ranvier. J Physiol 573:17–34.
55. Shah MM, Migliore M, Valencia I, Cooper EC, Brown DA (2008) Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons. Proc Natl Acad Sci USA 105:7869–7874.
56. Sicca F, Imbrici P, D’Adamo MC, Moro F, Bonatti F, Brovedani P, Grottesi A, Guerrini R, Masi G, Santorelli FM, PessiaM (2011) Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardly-rectifying K+ channel Kir4.1. Neurobiol Dis 43:239–247.
57. 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 chan- nel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat Genet 18:25–29.
58. Singh NA, Otto JF, Dahle EJ, Pappas C, Leslie JD, Vilaythong A, Noebels JL, White HS, Wilcox KS, Leppert MF (2008) Mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions show seizures and neuronal plasticity without synaptic reorganization. J Physiol 586:3405–3423.
59. Soldovieri MV, Castaldo P, Iodice L, Miceli F, Barrese V, Bellini G, Miraglia del Giudice E, Pascotto A, Bonatti S, Annunziato L, Taglialatela M (2006) Decreased subunit stability as a novel mechanism for potassium current impairment by a KCNQ2 C terminus mutation causing benign familial neonatal convulsions. J Biol Chem 281:418–428.
60. 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 27:4919–4928.
61. Soldovieri MV, Boutry-Kryza N, Milh M, Doummar D, Heron B, Bourel E, Ambrosino P, Miceli F, De Maria M, Dorison N, Auvin S, Echenne B, Oertel J, Riquet A, Lambert L, Gerard M, Roubergue A, Calender A, Mignot C, Taglialatela M, et al. (2014) 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 35:356–367.
62. Spruston N, Schiller Y, Stuart G, Sakmann B (1995) Activity dependent action potential invasion and calcium influx into hippocampal CAl den-drites. Science 268:297–300.
63. Steinlein OK, Conrad C, Weidner B (2007) Benign familial neonatal convulsions: always benign? Epilepsy Res 73:245–249.
64. Striano P, de Jonghe P, Zara F (2013) Genetic epileptic encephalopathies: is all written into the DNA? Epilepsia 54 [Suppl 8]:22–26.
65. Veeramah KR, Johnstone L, Karafet TM, Wolf D, Sprissler R, Salogiannis J, Barth-Maron A, Greenberg ME, Stuhlmann T, Weinert S, Jentsch TJ, Pazzi M, Restifo LL, Talwar D, Erickson RP, Hammer MF (2013) Exome sequencing reveals new causal mutations in children with epileptic en-cephalopathies. Epilepsia 54:1270–1281.
66. Vervaeke K, Gu N, Agdestein C, Hu H, Storm JF (2006) Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release. J Physiol 576:235–256.
67. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McK-innon D (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 282:1890–1893.
68. Weckhuysen S, Mandelstam S, Suls A, Audenaert D, Deconinck T, Claes LR, Deprez L, Smets K, Hristova D, Yordanova I, Jordanova A, Ceulemans B, Jansen A, Hasaerts D, Roelens F, Lagae L, Yendle S, Stanley T, Heron SE, Mulley JC, et al. (2012) KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 71:15–25.
69. Weckhuysen S, Ivanovic V, Hendrickx R, Van Coster R, Hjalgrim H, Møller RS, Grønborg S, Schoonjans AS, Ceulemans B, Heavin SB, Eltze C, Hor-vath R, Casara G, Pisano T, Giordano L, Rostasy K, Haberlandt E, Al-brecht B, Bevot A, Benkel I, et al. (2013) Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology 81:1697–1703.
70. Yang Y, Vasylyev DV, Dib-Hajj F, Veeramah KR, Hammer MF, Dib-Hajj SD, Waxman SG (2013) Multistate structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state. J Neurosci 33:16586-16593.
71. Zagotta WN, Aldrich RW (1990) Voltage-dependent gating of Shaker A-type potassium channels in Drosophila muscle. J Gen Physiol 95:29–60.
72. Zaika O, Hernandez CC, Bal M, Tolstykh GP, Shapiro MS (2008) Determinants within the turret and pore-loop domains of KCNQ3 K + channels governing functional activity. Biophys J 95:5121–5137.
73. Zemankovics R, Kali S, Paulsen O, Freund TF, Hajos N (2010) Differences in subthreshold resonance of hippocampal pyramidal cells and interneu-rons: the role of h-current and passive membrane characteristics. J Physiol 588:2109–2132.