| Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development. | Coupling of Slack and Na(V)1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development.
Yuan T, Wang Y, Jin Y, Yang H, Xu S, Zhang H, Chen Q, Li N, Ma X, Song H, Peng C, Geng Z, Dong J, Duan G, Sun Q, Yang Y, Yang F, Huang Z., Free PMC Article | 03/1/2024 |
| Functional evaluation of epilepsy-associated KCNT1 variants in multiple cellular systems reveals a predominant gain of function impact on channel properties. | Functional evaluation of epilepsy-associated KCNT1 variants in multiple cellular systems reveals a predominant gain of function impact on channel properties.
Hinckley CA, Zhu Z, Chu JH, Gubbels C, Danker T, Cherry JJ, Whelan CD, Engle SJ, Nguyen V. | 08/10/2023 |
| Functional Effects of Epilepsy Associated KCNT1 Mutations Suggest Pathogenesis via Aberrant Inhibitory Neuronal Activity. | Functional Effects of Epilepsy Associated KCNT1 Mutations Suggest Pathogenesis via Aberrant Inhibitory Neuronal Activity.
Rychkov GY, Shaukat Z, Lim CX, Hussain R, Roberts BJ, Bonardi CM, Rubboli G, Meaney BF, Whitney R, Møller RS, Ricos MG, Dibbens LM., Free PMC Article | 01/7/2023 |
| The phenotypic spectrum of KCNT1: a new family with variable epilepsy syndromes including mild focal epilepsy. | The phenotypic spectrum of KCNT1: a new family with variable epilepsy syndromes including mild focal epilepsy.
Cherian C, Appendino JP, Ashtiani S, Federico P, Molnar CP, Kerr M, Khan A, Au PYB, Klein KM. | 04/2/2022 |
| KCNT1-related epilepsies and epileptic encephalopathies: phenotypic and mutational spectrum. | KCNT1-related epilepsies and epileptic encephalopathies: phenotypic and mutational spectrum.
Bonardi CM, Heyne HO, Fiannacca M, Fitzgerald MP, Gardella E, Gunning B, Olofsson K, Lesca G, Verbeek N, Stamberger H, Striano P, Zara F, Mancardi MM, Nava C, Syrbe S, Buono S, Baulac S, Coppola A, Weckhuysen S, Schoonjans AS, Ceulemans B, Sarret C, Baumgartner T, Muhle H, Portes VD, Toulouse J, Nougues MC, Rossi M, Demarquay G, Ville D, Hirsch E, Maurey H, Willems M, de Bellescize J, Altuzarra CD, Villeneuve N, Bartolomei F, Picard F, Hornemann F, Koolen DA, Kroes HY, Reale C, Fenger CD, Tan WH, Dibbens L, Bearden DR, Møller RS, Rubboli G. | 02/26/2022 |
| Recurrent pulmonary hemorrhage in juvenile patients with KCNT1 mutation. | Recurrent pulmonary hemorrhage in juvenile patients with KCNT1 mutation.
Ikeda A, Ueda H, Matsui K, Iai M, Goto T. | 08/21/2021 |
| KCNT1 mutations lead to a severe form of epilepsy; this KCNT1 mutation was found to increase the Slack current in neurons. | An Epilepsy-Associated KCNT1 Mutation Enhances Excitability of Human iPSC-Derived Neurons by Increasing Slack K(Na) Currents.
Quraishi IH, Stern S, Mangan KP, Zhang Y, Ali SR, Mercier MR, Marchetto MC, McLachlan MJ, Jones EM, Gage FH, Kaczmarek LK., Free PMC Article | 06/27/2020 |
| Extracerebral symptoms probably linked with KCNT1 mutation were present, including arteriovenous fistula, dilated cardiomyopathy and precocious puberty. Eight patients (47%) had died at 3 (1.5-15.4) years including three from suspected sudden unexpected death in epilepsy. | KCNT1 epilepsy with migrating focal seizures shows a temporal sequence with poor outcome, high mortality and SUDEP.
Kuchenbuch M, Barcia G, Chemaly N, Carme E, Roubertie A, Gibaud M, Van Bogaert P, de Saint Martin A, Hirsch E, Dubois F, Sarret C, Nguyen The Tich S, Laroche C, des Portes V, Billette de Villemeur T, Barthez MA, Auvin S, Bahi-Buisson N, Desguerre I, Kaminska A, Benquet P, Nabbout R. | 06/20/2020 |
| that KCNT1 epileptogenicity may result not only from dysregulated excitability by controlling Na+K+ transport | Mild malformations of cortical development in sleep-related hypermotor epilepsy due to KCNT1 mutations.
Rubboli G, Plazzi G, Picard F, Nobili L, Hirsch E, Chelly J, Prayson RA, Boutonnat J, Bramerio M, Kahane P, Dibbens LM, Gardella E, Baulac S, Møller RS., Free PMC Article | 02/22/2020 |
| KCNT1 is likely to be a major gene causing early infantile epileptic encephalopathy type 14 | [Early infantile epileptic encephalopathy type 14: three cases of epilepsy in infancy with migrating focal seizures due to KCNT1 mutations].
Kholin AA, Zavadenko NN, Fedonyuk ID, Antonets AV, Mukhin KY, Malov AG, Vshivkov MI, Anisimov GV, Il'ina ES. | 11/9/2019 |
| Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. | Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy.
McTague A, Nair U, Malhotra S, Meyer E, Trump N, Gazina EV, Papandreou A, Ngoh A, Ackermann S, Ambegaonkar G, Appleton R, Desurkar A, Eltze C, Kneen R, Kumar AV, Lascelles K, Montgomery T, Ramesh V, Samanta R, Scott RH, Tan J, Whitehouse W, Poduri A, Scheffer IE, Chong WKK, Cross JH, Topf M, Petrou S, Kurian MA., Free PMC Article | 07/27/2019 |
| studied the mutational characteristics of KCNT1 and its clinical features in children with early-onset epileptic encephalopathy;the mutation of KCNT1 gene is mainly de novo. The onset of the disease was early, and mostly occurs in neonate and early infancy | [Genetic and clinical analysis of children with early-onset epilepsy encephalopathy caused by KCNT1 gene mutation].
Chen Y, Bao XH, Zhang QP, Wang JP, Wen YX, Yu SJ, Zhao Y. | 04/6/2019 |
| G288S missense mutation, associated with seizures and neurodevelopmental delay resulted in larger whole cell K+ currents compared with wild-type KCNT1 currents. | Lethal digenic mutations in the K(+) channels Kir4.1 (KCNJ10) and SLACK (KCNT1) associated with severe-disabling seizures and neurodevelopmental delay.
Hasan S, Balobaid A, Grottesi A, Dabbagh O, Cenciarini M, Rawashdeh R, Al-Sagheir A, Bove C, Macchioni L, Pessia M, Al-Owain M, D'Adamo MC., Free PMC Article | 06/2/2018 |
| Case report describing 3 infants with malignant migrating partial seizures with KCNT1 mutations accompanied by massive systemic to pulmonary collateral arteries. | Three Cases of KCNT1 Mutations: Malignant Migrating Partial Seizures in Infancy with Massive Systemic to Pulmonary Collateral Arteries.
Kawasaki Y, Kuki I, Ehara E, Murakami Y, Okazaki S, Kawawaki H, Hara M, Watanabe Y, Kishimoto S, Suda K, Saitsu H, Matsumoto N. | 12/16/2017 |
| Stimulation of Slack K(+) channels alters mass at the plasma membrane by triggering dissociation of Phactr-1. | Stimulation of Slack K(+) Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex.
Fleming MR, Brown MR, Kronengold J, Zhang Y, Jenkins DP, Barcia G, Nabbout R, Bausch AE, Ruth P, Lukowski R, Navaratnam DS, Kaczmarek LK., Free PMC Article | 11/18/2017 |
| In the present study, we evaluated two other potential mechanisms for stabilization of Slo2 channels in a closed state: (1) dewetting and collapse of the inner pore (hydrophobic gating) and (2) constriction of the inner pore by tight criss-crossing of the cytoplasmic ends of the S6 alpha-helical segments. | Molecular mechanisms of Slo2 K(+) channel closure.
Giese MH, Gardner A, Hansen A, Sanguinetti MC., Free PMC Article | 09/23/2017 |
| two de novo, heterozygous KCNT1 mutations were identified in two unrelated malignant migrating partial seizures probands. Both mutations induced a marked leftward shift in homomeric channel activation gating. | Characterization of two de novoKCNT1 mutations in children with malignant migrating partial seizures in infancy.
Rizzo F, Ambrosino P, Guacci A, Chetta M, Marchese G, Rocco T, Soldovieri MV, Manocchio L, Mosca I, Casara G, Vecchi M, Taglialatela M, Coppola G, Weisz A. | 12/24/2016 |
| Better understanding of the mechanisms underlying KCNT1-related disease will produce further improvements in treatment of the associated severe seizure disorders. | KCNT1 mutations in seizure disorders: the phenotypic spectrum and functional effects.
Lim CX, Ricos MG, Dibbens LM, Heron SE. | 12/17/2016 |
| The sodium sensitivity of these epilepsy causing mutants probably determines the [Na(+)]i concentration at which these mutants exert their pathological effects. | Epilepsy-Related Slack Channel Mutants Lead to Channel Over-Activity by Two Different Mechanisms.
Tang QY, Zhang FF, Xu J, Wang R, Chen J, Logothetis DE, Zhang Z., Free PMC Article | 10/1/2016 |
| We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than nocturnal frontal lobe epilepsy and malignant migrating focal seizures of infancy. | Mutations in KCNT1 cause a spectrum of focal epilepsies.
Møller RS, Heron SE, Larsen LH, Lim CX, Ricos MG, Bayly MA, van Kempen MJ, Klinkenberg S, Andrews I, Kelley K, Ronen GM, Callen D, McMahon JM, Yendle SC, Carvill GL, Mefford HC, Nabbout R, Poduri A, Striano P, Baglietto MG, Zara F, Smith NJ, Pridmore C, Gardella E, Nikanorova M, Dahl HA, Gellert P, Scheffer IE, Gunning B, Kragh-Olsen B, Dibbens LM., Free PMC Article | 04/30/2016 |
| This study demonstrate that KCNT1 mutations are strongly associated with early-onset epileptic encephalopathy. | De novo KCNT1 mutations in early-onset epileptic encephalopathy.
Ohba C, Kato M, Takahashi N, Osaka H, Shiihara T, Tohyama J, Nabatame S, Azuma J, Fujii Y, Hara M, Tsurusawa R, Inoue T, Ogata R, Watanabe Y, Togashi N, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Saitsu H, Matsumoto N. | 04/30/2016 |
| Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three Brugada syndrome patients (20%) | Disease-targeted sequencing of ion channel genes identifies de novo mutations in patients with non-familial Brugada syndrome.
Juang JM, Lu TP, Lai LC, Ho CC, Liu YB, Tsai CT, Lin LY, Yu CC, Chen WJ, Chiang FT, Yeh SF, Lai LP, Chuang EY, Lin JL., Free PMC Article | 10/31/2015 |
| Nine different mutations of the KCNT1 (Slack) Na(+)-activated K(+) channel give rise to three distinct forms of epilepsy. | Human slack potassium channel mutations increase positive cooperativity between individual channels.
Kim GE, Kronengold J, Barcia G, Quraishi IH, Martin HC, Blair E, Taylor JC, Dulac O, Colleaux L, Nabbout R, Kaczmarek LK., Free PMC Article | 08/22/2015 |
| Slick channels, in contrast to the similar Slack channels, are the only high-conductance K+ channels strongly sensitive to small changes in cell volume. | Cell volume changes regulate slick (Slo2.1), but not slack (Slo2.2) K+ channels.
Tejada MA, Stople K, Hammami Bomholtz S, Meinild AK, Poulsen AN, Klaerke DA., Free PMC Article | 06/27/2015 |
| Genetic studies reveal two novel genes for Ohtahara Syndrome: KCNT1 and PIGQ. | Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis.
Martin HC, Kim GE, Pagnamenta AT, Murakami Y, Carvill GL, Meyer E, Copley RR, Rimmer A, Barcia G, Fleming MR, Kronengold J, Brown MR, Hudspith KA, Broxholme J, Kanapin A, Cazier JB, Kinoshita T, Nabbout R, WGS500 Consortium, Bentley D, McVean G, Heavin S, Zaiwalla Z, McShane T, Mefford HC, Shears D, Stewart H, Kurian MA, Scheffer IE, Blair E, Donnelly P, Kaczmarek LK, Taylor JC., Free PMC Article | 01/17/2015 |