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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

General Review Article

Double-edged Role of KNa Channels in Brain Tuning: Identifying Epileptogenic Network Micro-Macro Disconnection

Author(s): Ru Liu, Lei Sun, Yunfu Wang, Meng Jia, Qun Wang, Xiang Cai* and Jianping Wu*

Volume 20, Issue 5, 2022

Published on: 29 March, 2022

Page: [916 - 928] Pages: 13

DOI: 10.2174/1570159X19666211215104829

Price: $65

Open Access Journals Promotions 2
Abstract

Epilepsy is commonly recognized as a disease driven by generalized hyperexcited and hypersynchronous neural activity. Sodium-activated potassium channels (KNa channels), which are encoded by the Slo 2.2 and Slo 2.1 genes, are widely expressed in the central nervous system and considered as “brakes” to adjust neuronal adaptation through regulating action potential threshold or after-hyperpolarization under physiological condition. However, the variants in KNa channels, especially gain-of-function variants, have been found in several childhood epileptic conditions. Most previous studies focused on mapping the epileptic network on the macroscopic scale while ignoring the value of microscopic changes. Notably, paradoxical role of KNa channels working on individual neuron/microcircuit and the macroscopic epileptic expression highlights the importance of understanding epileptogenic network through combining microscopic and macroscopic methods. Here, we first illustrated the molecular and physiological function of KNa channels on preclinical seizure models and patients with epilepsy. Next, we summarized current hypothesis on the potential role of KNa channels during seizures to provide essential insight into what emerged as a micro-macro disconnection at different levels. Additionally, we highlighted the potential utility of KNa channels as therapeutic targets for developing innovative anti-seizure medications.

Keywords: Epilepsy, KNa channels, microcircuit, rhythm, micro-macro disconnection, quinidine.

Graphical Abstract
[1]
Thijs, R.D.; Surges, R.; O’Brien, T.J.; Sander, J.W. Epilepsy in adults. Lancet, 2019, 393(10172), 689-701.
[http://dx.doi.org/10.1016/S0140-6736(18)32596-0] [PMID: 30686584]
[2]
Fisher, R.S.; Acevedo, C.; Arzimanoglou, A.; Bogacz, A.; Cross, J.H.; Elger, C.E.; Engel, J., Jr; Forsgren, L.; French, J.A.; Glynn, M.; Hesdorffer, D.C.; Lee, B.I.; Mathern, G.W.; Moshé, S.L.; Perucca, E.; Scheffer, I.E.; Tomson, T.; Watanabe, M.; Wiebe, S. ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 2014, 55(4), 475-482.
[http://dx.doi.org/10.1111/epi.12550] [PMID: 24730690]
[3]
Wallace, H.; Shorvon, S.; Tallis, R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922 and age-specific fertility rates of women with epilepsy. Lancet, 1998, 352(9145), 1970-1973.
[http://dx.doi.org/10.1016/S0140-6736(98)04512-7] [PMID: 9872246]
[4]
Kwan, P.; Arzimanoglou, A.; Berg, A.T.; Brodie, M.J.; Allen Hauser, W.; Mathern, G.; Moshe, S.L.; Perucca, E.; Wiebe, S.; French, J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia, 2010, 51(6), 1069-1077.
[http://dx.doi.org/10.1111/j.1528-1167.2009.02397.x] [PMID: 19889013]
[5]
Jette, N.; Reid, A.Y.; Wiebe, S. Surgical management of epilepsy. CMAJ, 2014, 186(13), 997-1004.
[http://dx.doi.org/10.1503/cmaj.121291] [PMID: 24914117]
[6]
Boison, D.; Steinhäuser, C. Epilepsy and astrocyte energy metabolism. Glia, 2018, 66(6), 1235-1243.
[http://dx.doi.org/10.1002/glia.23247] [PMID: 29044647]
[7]
Farrell, J.S.; Nguyen, Q.A.; Soltesz, I. Resolving the micro-macro disconnect to address core features of seizure networks. Neuron, 2019, 101(6), 1016-1028.
[http://dx.doi.org/10.1016/j.neuron.2019.01.043] [PMID: 30897354]
[8]
Stuart, G.; Spruston, N.; Sakmann, B.; Häusser, M. Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends Neurosci., 1997, 20(3), 125-131.
[http://dx.doi.org/10.1016/S0166-2236(96)10075-8] [PMID: 9061867]
[9]
Barcia, G.; Fleming, M.R.; Deligniere, A.; Gazula, V.R.; Brown, M.R.; Langouet, M.; Chen, H.; Kronengold, J.; Abhyankar, A.; Cilio, R.; Nitschke, P.; Kaminska, A.; Boddaert, N.; Casanova, J.L.; Desguerre, I.; Munnich, A.; Dulac, O.; Kaczmarek, L.K.; Colleaux, L.; Nabbout, R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat. Genet., 2012, 44(11), 1255-1259.
[http://dx.doi.org/10.1038/ng.2441] [PMID: 23086397]
[10]
Heron, S.E.; Smith, K.R.; Bahlo, M.; Nobili, L.; Kahana, E.; Licchetta, L.; Oliver, K.L.; Mazarib, A.; Afawi, Z.; Korczyn, A.; Plazzi, G.; Petrou, S.; Berkovic, S.F.; Scheffer, I.E.; Dibbens, L.M. Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy. Nat. Genet., 2012, 44(11), 1188-1190.
[http://dx.doi.org/10.1038/ng.2440] [PMID: 23086396]
[11]
Rizzo, F.; Ambrosino, P.; Guacci, A.; Chetta, M.; Marchese, G.; Rocco, T.; Soldovieri, M.V.; Manocchio, L.; Mosca, I.; Casara, G.; Vecchi, M.; Taglialatela, M.; Coppola, G.; Weisz, A. Characterization of two de novoKCNT1 mutations in children with malignant migrating partial seizures in infancy. Mol. Cell. Neurosci., 2016, 72, 54-63.
[http://dx.doi.org/10.1016/j.mcn.2016.01.004] [PMID: 26784557]
[12]
Ambrosino, P.; Soldovieri, M.V.; Bast, T.; Turnpenny, P.D.; Uhrig, S.; Biskup, S.; Döcker, M.; Fleck, T.; Mosca, I.; Manocchio, L.; Iraci, N.; Taglialatela, M.; Lemke, J.R. De novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy. Ann. Neurol., 2018, 83(6), 1198-1204.
[http://dx.doi.org/10.1002/ana.25248] [PMID: 29740868]
[13]
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. De novo KCNT1 mutations in early-onset epileptic encephalopathy. Epilepsia, 2015, 56(9), e121-e128.
[http://dx.doi.org/10.1111/epi.13072] [PMID: 26140313]
[14]
Gururaj, S.; Palmer, E.E.; Sheehan, G.D.; Kandula, T.; Macintosh, R.; Ying, K.; Morris, P.; Tao, J.; Dias, K.R.; Zhu, Y.; Dinger, M.E.; Cowley, M.J.; Kirk, E.P.; Roscioli, T.; Sachdev, R.; Duffey, M.E.; Bye, A.; Bhattacharjee, A. A de novo mutation in the sodium-activated potassium channel KCNT2 alters ion selectivity and causes epileptic encephalopathy. Cell Rep., 2017, 21(4), 926-933.
[http://dx.doi.org/10.1016/j.celrep.2017.09.088] [PMID: 29069600]
[15]
Fukuoka, M.; Kuki, I.; Kawawaki, H.; Okazaki, S.; Kim, K.; Hattori, Y.; Tsuji, H.; Nukui, M.; Inoue, T.; Yoshida, Y.; Uda, T.; Kimura, S.; Mogami, Y.; Suzuki, Y.; Okamoto, N.; Saitsu, H.; Matsumoto, N. Quinidine therapy for West syndrome with KCNTI mutation: A case report. Brain Dev., 2017, 39(1), 80-83.
[http://dx.doi.org/10.1016/j.braindev.2016.08.002] [PMID: 27578169]
[16]
Martinez-Espinosa, P.L.; Wu, J.; Yang, C.; Gonzalez-Perez, V.; Zhou, H.; Liang, H.; Xia, X.M.; Lingle, C.J. Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons. eLife, 2015, 4, e10013.
[http://dx.doi.org/10.7554/eLife.10013] [PMID: 26559620]
[17]
Shore, A.N.; Colombo, S.; Tobin, W.F.; Petri, S.; Cullen, E.R.; Dominguez, S.; Bostick, C.D.; Beaumont, M.A.; Williams, D.; Khodagholy, D.; Yang, M.; Lutz, C.M.; Peng, Y.; Gelinas, J.N.; Goldstein, D.B.; Boland, M.J.; Frankel, W.N.; Weston, M.C. Reduced GABAergic neuron excitability, altered synaptic connectivity, and seizures in a KCNT1 gain-of-function mouse model of childhood epilepsy. Cell Rep., 2020, 33(4), 108303.
[http://dx.doi.org/10.1016/j.celrep.2020.108303] [PMID: 33113364]
[18]
Paz, J.T.; Huguenard, J.R. Microcircuits and their interactions in epilepsy: is the focus out of focus? Nat. Neurosci., 2015, 18(3), 351-359.
[http://dx.doi.org/10.1038/nn.3950] [PMID: 25710837]
[19]
Kameyama, M.; Kakei, M.; Sato, R.; Shibasaki, T.; Matsuda, H.; Irisawa, H. Intracellular Na+ activates a K+ channel in mammalian cardiac cells. Nature, 1984, 309(5966), 354-356.
[http://dx.doi.org/10.1038/309354a0] [PMID: 6328309]
[20]
Bader, C.R.; Bernheim, L.; Bertrand, D. Sodium-activated potassium current in cultured avian neurones. Nature, 1985, 317(6037), 540-542.
[http://dx.doi.org/10.1038/317540a0] [PMID: 2413369]
[21]
Yuan, A.; Santi, C.M.; Wei, A.; Wang, Z.W.; Pollak, K.; Nonet, M.; Kaczmarek, L.; Crowder, C.M.; Salkoff, L. The sodium-activated potassium channel is encoded by a member of the Slo gene family. Neuron, 2003, 37(5), 765-773.
[http://dx.doi.org/10.1016/S0896-6273(03)00096-5] [PMID: 12628167]
[22]
Bhattacharjee, A.; Joiner, W.J.; Wu, M.; Yang, Y.; Sigworth, F.J.; Kaczmarek, L.K. Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP. J. Neurosci., 2003, 23(37), 11681-11691.
[http://dx.doi.org/10.1523/JNEUROSCI.23-37-11681.2003] [PMID: 14684870]
[23]
Jiang, Y.; Pico, A.; Cadene, M.; Chait, B.T.; MacKinnon, R. Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel. Neuron, 2001, 29(3), 593-601.
[http://dx.doi.org/10.1016/S0896-6273(01)00236-7] [PMID: 11301020]
[24]
Rizzi, S.; Knaus, H.G.; Schwarzer, C. Differential distribution of the sodium-activated potassium channels slick and slack in mouse brain. J. Comp. Neurol., 2016, 524(10), 2093-2116.
[http://dx.doi.org/10.1002/cne.23934] [PMID: 26587966]
[25]
Hite, R.K.; MacKinnon, R. Structural titration of Slo2.2, a Na+-dependent K+ channel. Cell, 2017, 168(3), 390-399.e11.
[http://dx.doi.org/10.1016/j.cell.2016.12.030] [PMID: 28111072]
[26]
Brown, M.R.; Kronengold, J.; Gazula, V.R.; Spilianakis, C.G.; Flavell, R.A.; von Hehn, C.A.; Bhattacharjee, A.; Kaczmarek, L.K. Amino-termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation. J. Physiol., 2008, 586(21), 5161-5179.
[http://dx.doi.org/10.1113/jphysiol.2008.160861] [PMID: 18787033]
[27]
Bhattacharjee, A.; Gan, L.; Kaczmarek, L.K. Localization of the Slack potassium channel in the rat central nervous system. J. Comp. Neurol., 2002, 454(3), 241-254.
[http://dx.doi.org/10.1002/cne.10439] [PMID: 12442315]
[28]
Bhattacharjee, A.; von Hehn, C.A.; Mei, X.; Kaczmarek, L.K. Localization of the Na+-activated K+ channel Slick in the rat central nervous system. J. Comp. Neurol., 2005, 484(1), 80-92.
[http://dx.doi.org/10.1002/cne.20462] [PMID: 15717307]
[29]
Evely, K.M.; Pryce, K.D.; Bausch, A.E.; Lukowski, R.; Ruth, P.; Haj-Dahmane, S.; Bhattacharjee, A. Slack KNa channels influence dorsal horn synapses and nociceptive behavior. Mol. Pain, 2017, 13, 1744806917714342.
[http://dx.doi.org/10.1177/1744806917714342] [PMID: 28604221]
[30]
Schwindt, P.C.; Spain, W.J.; Crill, W.E. Long-lasting reduction of excitability by a sodium-dependent potassium current in cat neocortical neurons. J. Neurophysiol., 1989, 61(2), 233-244.
[http://dx.doi.org/10.1152/jn.1989.61.2.233] [PMID: 2918352]
[31]
Kim, G.E.; Kronengold, J.; Barcia, G.; Quraishi, I.H.; Martin, H.C.; Blair, E.; Taylor, J.C.; Dulac, O.; Colleaux, L.; Nabbout, R.; Kaczmarek, L.K. Human slack potassium channel mutations increase positive cooperativity between individual channels. Cell Rep., 2014, 9(5), 1661-1672.
[http://dx.doi.org/10.1016/j.celrep.2014.11.015] [PMID: 25482562]
[32]
Joiner, W.J.; Tang, M.D.; Wang, L.Y.; Dworetzky, S.I.; Boissard, C.G.; Gan, L.; Joiner, W.J.; Tang, M.D.; Wang, L.Y.; Dworetzky, S.I.; Boissard, C.G.; Gan, L.; Gribkoff, V.K.; Kaczmarek, L.K. Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat. Neurosci., 1998, 1(6), 462-469.
[http://dx.doi.org/10.1038/2176] [PMID: 10196543]
[33]
Xu, N.L. Deciphering pyramidal neuron diversity: delineating perceptual functions of projection-defined neuronal types. Neuron, 2020, 105(2), 209-211.
[http://dx.doi.org/10.1016/j.neuron.2019.12.018] [PMID: 31972143]
[34]
Chen, H.; Kronengold, J.; Yan, Y.; Gazula, V.R.; Brown, M.R.; Ma, L.; Ferreira, G.; Yang, Y.; Bhattacharjee, A.; Sigworth, F.J.; Salkoff, L.; Kaczmarek, L.K. The N-terminal domain of Slack determines the formation and trafficking of Slick/Slack heteromeric sodium-activated potassium channels. J. Neurosci., 2009, 29(17), 5654-5665.
[http://dx.doi.org/10.1523/JNEUROSCI.5978-08.2009] [PMID: 19403831]
[35]
Hu, H.; Vervaeke, K.; Storm, J.F. 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., 2007, 27(8), 1853-1867.
[http://dx.doi.org/10.1523/JNEUROSCI.4463-06.2007] [PMID: 17314282]
[36]
Franceschetti, S.; Lavazza, T.; Curia, G.; Aracri, P.; Panzica, F.; Sancini, G.; Avanzini, G.; Magistretti, J. Na+-activated K+ current contributes to postexcitatory hyperpolarization in neocortical intrinsically bursting neurons. J. Neurophysiol., 2003, 89(4), 2101-2111.
[http://dx.doi.org/10.1152/jn.00695.2002] [PMID: 12686580]
[37]
Liu, X.; Stan Leung, L. Sodium-activated potassium conductance participates in the depolarizing afterpotential following a single action potential in rat hippocampal CA1 pyramidal cells. Brain Res., 2004, 1023(2), 185-192.
[http://dx.doi.org/10.1016/j.brainres.2004.07.017] [PMID: 15374744]
[38]
Wallén, P.; Robertson, B.; Cangiano, L.; Löw, P.; Bhattacharjee, A.; Kaczmarek, L.K.; Grillner, S. Sodium-dependent potassium channels of a Slack-like subtype contribute to the slow afterhyperpolarization in lamprey spinal neurons. J. Physiol., 2007, 585(Pt 1), 75-90.
[http://dx.doi.org/10.1113/jphysiol.2007.138156] [PMID: 17884929]
[39]
Kim, U.; McCormick, D.A. Functional and ionic properties of a slow afterhyperpolarization in ferret perigeniculate neurons in vitro. J. Neurophysiol., 1998, 80(3), 1222-1235.
[http://dx.doi.org/10.1152/jn.1998.80.3.1222] [PMID: 9744934]
[40]
Yang, B.; Desai, R.; Kaczmarek, L.K. Slack and Slick K(Na) channels regulate the accuracy of timing of auditory neurons. J. Neurosci., 2007, 27(10), 2617-2627.
[http://dx.doi.org/10.1523/JNEUROSCI.5308-06.2007] [PMID: 17344399]
[41]
Kaczmarek, L.K. Slack, slick and sodium-activated potassium channels. ISRN Neurosci., 2013, 2013(2013), , 2013.
[http://dx.doi.org/10.1155/2013/354262] [PMID: 24319675]
[42]
Reijntjes, D.O.J.; Lee, J.H.; Park, S.; Schubert, N.M.A.; van Tuinen, M.; Vijayakumar, S.; Jones, T.A.; Jones, S.M.; Gratton, M.A.; Xia, X.M.; Yamoah, E.N.; Pyott, S.J. Sodium-activated potassium channels shape peripheral auditory function and activity of the primary auditory neurons in mice. Sci. Rep., 2019, 9(1), 2573.
[http://dx.doi.org/10.1038/s41598-019-39119-z] [PMID: 30796290]
[43]
Hage, T.A.; Salkoff, L. Sodium-activated potassium channels are functionally coupled to persistent sodium currents. J. Neurosci., 2012, 32(8), 2714-2721.
[http://dx.doi.org/10.1523/JNEUROSCI.5088-11.2012] [PMID: 22357855]
[44]
Budelli, G.; Hage, T.A.; Wei, A.; Rojas, P.; Jong, Y.J.; O’Malley, K.; Salkoff, L. Na+-activated K+ channels express a large delayed outward current in neurons during normal physiology. Nat. Neurosci., 2009, 12(6), 745-750.
[http://dx.doi.org/10.1038/nn.2313] [PMID: 19412167]
[45]
Stafstrom, C.E. Persistent sodium current and its role in epilepsy. Epilepsy Curr., 2007, 7(1), 15-22.
[http://dx.doi.org/10.1111/j.1535-7511.2007.00156.x] [PMID: 17304346]
[46]
Igelström, K.M. Is slack an intrinsic seizure terminator? Neuroscientist, 2013, 19(3), 248-254.
[http://dx.doi.org/10.1177/1073858412446311] [PMID: 22645110]
[47]
Kaczmarek, L.K. Non-conducting functions of voltage-gated ion channels. Nat. Rev. Neurosci., 2006, 7(10), 761-771.
[http://dx.doi.org/10.1038/nrn1988] [PMID: 16988652]
[48]
Brown, M.R.; Kronengold, J.; Gazula, V.R.; Chen, Y.; Strumbos, J.G.; Sigworth, F.J.; Navaratnam, D.; Kaczmarek, L.K. Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack. Nat. Neurosci., 2010, 13(7), 819-821.
[http://dx.doi.org/10.1038/nn.2563] [PMID: 20512134]
[49]
Zhang, Y.; Brown, M.R.; Hyland, C.; Chen, Y.; Kronengold, J.; Fleming, M.R.; Kohn, A.B.; Moroz, L.L.; Kaczmarek, L.K. Regulation of neuronal excitability by interaction of fragile X mental retardation protein with slack potassium channels. J. Neurosci., 2012, 32(44), 15318-15327.
[http://dx.doi.org/10.1523/JNEUROSCI.2162-12.2012] [PMID: 23115170]
[50]
Huang, F.; Wang, X.; Ostertag, E.M.; Nuwal, T.; Huang, B.; Jan, Y.N.; Basbaum, A.I.; Jan, L.Y. TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and regulates pain processing. Nat. Neurosci., 2013, 16(9), 1284-1290.
[http://dx.doi.org/10.1038/nn.3468] [PMID: 23872594]
[51]
Fleming, M.R.; Brown, M.R.; Kronengold, J.; Zhang, Y.; Jenkins, D.P.; Barcia, G.; Nabbout, R.; Bausch, A.E.; Ruth, P.; Lukowski, R.; Navaratnam, D.S.; Kaczmarek, L.K. Stimulation of slack K(+) channels alters mass at the plasma membrane by triggering dissociation of a phosphatase-regulatory complex. Cell Rep., 2016, 16(9), 2281-2288.
[http://dx.doi.org/10.1016/j.celrep.2016.07.024] [PMID: 27545877]
[52]
Uchino, S.; Wada, H.; Honda, S.; Hirasawa, T.; Yanai, S.; Nakamura, Y.; Ondo, Y.; Kohsaka, S. Slo2 sodium-activated K+ channels bind to the PDZ domain of PSD-95. Biochem. Biophys. Res. Commun., 2003, 310(4), 1140-1147.
[http://dx.doi.org/10.1016/j.bbrc.2003.09.133] [PMID: 14559234]
[53]
Allen, P.B.; Greenfield, A.T.; Svenningsson, P.; Haspeslagh, D.C.; Greengard, P. Phactrs 1-4: A family of protein phosphatase 1 and actin regulatory proteins. Proc. Natl. Acad. Sci. USA, 2004, 101(18), 7187-7192.
[http://dx.doi.org/10.1073/pnas.0401673101] [PMID: 15107502]
[54]
Ali, S.R.; Malone, T.J.; Zhang, Y.; Prechova, M.; Kaczmarek, L.K. Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1). FASEB J., 2020, 34(1), 1591-1601.
[http://dx.doi.org/10.1096/fj.201902366R] [PMID: 31914597]
[55]
Hamada, N.; Ogaya, S.; Nakashima, M.; Nishijo, T.; Sugawara, Y.; Iwamoto, I.; Ito, H.; Maki, Y.; Shirai, K.; Baba, S.; Maruyama, K.; Saitsu, H.; Kato, M.; Matsumoto, N.; Momiyama, T.; Nagata, K.I. De novo PHACTR1 mutations in West syndrome and their pathophysiological effects. Brain, 2018, 141(11), 3098-3114.
[http://dx.doi.org/10.1093/brain/awy246] [PMID: 30256902]
[56]
de Ligt, J.; Willemsen, M.H.; van Bon, B.W.; Kleefstra, T.; Yntema, H.G.; Kroes, T.; Vulto-van Silfhout, A.T.; Koolen, D.A.; de Vries, P.; Gilissen, C.; del Rosario, M.; Hoischen, A.; Scheffer, H.; de Vries, B.B.; Brunner, H.G.; Veltman, J.A.; Vissers, L.E. Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med., 2012, 367(20), 1921-1929.
[http://dx.doi.org/10.1056/NEJMoa1206524] [PMID: 23033978]
[57]
Kim, J.Y.; Choi, S.Y.; Moon, Y.; Kim, H.J.; Chin, J.H.; Kim, H.; Sun, W. Different expression patterns of Phactr family members in normal and injured mouse brain. Neuroscience, 2012, 221, 37-46.
[http://dx.doi.org/10.1016/j.neuroscience.2012.06.059] [PMID: 22766235]
[58]
Zheng, C.Y.; Seabold, G.K.; Horak, M.; Petralia, R.S. MAGUKs, synaptic development, and synaptic plasticity. Neuroscientist, 2011, 17(5), 493-512.
[http://dx.doi.org/10.1177/1073858410386384] [PMID: 21498811]
[59]
Zhang, P.; Lisman, J.E. Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons. J. Neurophysiol., 2012, 107(4), 1058-1066.
[http://dx.doi.org/10.1152/jn.00526.2011] [PMID: 22114157]
[60]
Ryan, D.P.; Ptácek, L.J. Episodic neurological channelopathies. Neuron, 2010, 68(2), 282-292.
[http://dx.doi.org/10.1016/j.neuron.2010.10.008] [PMID: 20955935]
[61]
Mao, X.; Bruneau, N.; Gao, Q.; Becq, H.; Jia, Z.; Xi, H.; Shu, L.; Wang, H.; Szepetowski, P.; Aniksztejn, L. The epilepsy of infancy with migrating focal seizures: identification of de novo mutations of the KCNT2 gene that exert inhibitory effects on the corresponding heteromeric KNa1.1/KNa1.2 potassium channel. Front. Cell. Neurosci., 2020, 14, 1.
[http://dx.doi.org/10.3389/fncel.2020.00001] [PMID: 32038177]
[62]
Milligan, C.J.; Li, M.; Gazina, E.V.; Heron, S.E.; Nair, U.; Trager, C.; Reid, C.A.; Venkat, A.; Younkin, D.P.; Dlugos, D.J.; Petrovski, S.; Goldstein, D.B.; Dibbens, L.M.; Scheffer, I.E.; Berkovic, S.F.; Petrou, S. KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine. Ann. Neurol., 2014, 75(4), 581-590.
[http://dx.doi.org/10.1002/ana.24128] [PMID: 24591078]
[63]
Tang, Q.Y.; Zhang, F.F.; Xu, J.; Wang, R.; Chen, J.; Logothetis, D.E.; Zhang, Z. Epilepsy-related slack channel mutants lead to channel over-activity by two different mechanisms. Cell Rep., 2016, 14(1), 129-139.
[http://dx.doi.org/10.1016/j.celrep.2015.12.019] [PMID: 26725113]
[64]
Brown, M.R.; Kaczmarek, L.K. Potassium channel modulation and auditory processing. Hear. Res., 2011, 279(1-2), 32-42.
[http://dx.doi.org/10.1016/j.heares.2011.03.004] [PMID: 21414395]
[65]
Fernández de Sevilla, D.; Garduño, J.; Galván, E.; Buño, W. Calcium-activated afterhyperpolarizations regulate synchronization and timing of epileptiform bursts in hippocampal CA3 pyramidal neurons. J. Neurophysiol., 2006, 96(6), 3028-3041.
[http://dx.doi.org/10.1152/jn.00434.2006] [PMID: 16971683]
[66]
Zhang, Z.; Rosenhouse-Dantsker, A.; Tang, Q.Y.; Noskov, S.; Logothetis, D.E. The RCK2 domain uses a coordination site present in Kir channels to confer sodium sensitivity to Slo2.2 channels. J. Neurosci., 2010, 30(22), 7554-7562.
[http://dx.doi.org/10.1523/JNEUROSCI.0525-10.2010] [PMID: 20519529]
[67]
Descalzo, V.F.; Nowak, L.G.; Brumberg, J.C.; McCormick, D.A.; Sanchez-Vives, M.V. Slow adaptation in fast-spiking neurons of visual cortex. J. Neurophysiol., 2005, 93(2), 1111-1118.
[http://dx.doi.org/10.1152/jn.00658.2004] [PMID: 15385594]
[68]
Quraishi, I.H.; Stern, S.; Mangan, K.P.; Zhang, Y.; Ali, S.R.; Mercier, M.R.; Marchetto, M.C.; McLachlan, M.J.; Jones, E.M.; Gage, F.H.; Kaczmarek, L.K. An epilepsy-associated KCNT1 mutation enhances excitability of human iPSC-derived neurons by increasing slack KNa currents. J. Neurosci., 2019, 39(37), 7438-7449.
[http://dx.doi.org/10.1523/JNEUROSCI.1628-18.2019] [PMID: 31350261]
[69]
Kuchenbuch, M.; Nabbout, R.; Yochum, M.; Sauleau, P.; Modolo, J.; Wendling, F.; Benquet, P. In silico model reveals the key role of GABA in KCNT1-epilepsy in infancy with migrating focal seizures. Epilepsia, 2021, 62(3), 683-697.
[http://dx.doi.org/10.1111/epi.16834] [PMID: 33617692]
[70]
Katz, L.C.; Shatz, C.J. Synaptic activity and the construction of cortical circuits. Science, 1996, 274(5290), 1133-1138.
[http://dx.doi.org/10.1126/science.274.5290.1133] [PMID: 8895456]
[71]
Sanchez-Vives, M.V.; Nowak, L.G.; McCormick, D.A. Cellular mechanisms of long-lasting adaptation in visual cortical neurons in vitro. J. Neurosci., 2000, 20(11), 4286-4299.
[http://dx.doi.org/10.1523/JNEUROSCI.20-11-04286.2000] [PMID: 10818164]
[72]
Møller, R.S.; Heron, S.E.; Larsen, L.H.; Lim, C.X.; Ricos, M.G.; Bayly, M.A.; van Kempen, M.J.; Klinkenberg, S.; Andrews, I.; Kelley, K.; Ronen, G.M.; Callen, D.; McMahon, J.M.; Yendle, S.C.; Carvill, G.L.; Mefford, H.C.; Nabbout, R.; Poduri, A.; Striano, P.; Baglietto, M.G.; Zara, F.; Smith, N.J.; Pridmore, C.; Gardella, E.; Nikanorova, M.; Dahl, H.A.; Gellert, P.; Scheffer, I.E.; Gunning, B.; Kragh-Olsen, B.; Dibbens, L.M. Mutations in KCNT1 cause a spectrum of focal epilepsies. Epilepsia, 2015, 56(9), e114-e120.
[http://dx.doi.org/10.1111/epi.13071] [PMID: 26122718]
[73]
Mikati, M.A.; Jiang, Y.H.; Carboni, M.; Shashi, V.; Petrovski, S.; Spillmann, R.; Milligan, C.J.; Li, M.; Grefe, A.; McConkie, A.; Berkovic, S.; Scheffer, I.; Mullen, S.; Bonner, M.; Petrou, S.; Goldstein, D. Quinidine in the treatment of KCNT1-positive epilepsies. Ann. Neurol., 2015, 78(6), 995-999.
[http://dx.doi.org/10.1002/ana.24520] [PMID: 26369628]
[74]
Evely, K.M.; Pryce, K.D.; Bhattacharjee, A. The Phe932Ile mutation in KCNT1 channels associated with severe epilepsy, delayed myelination and leukoencephalopathy produces a loss-of-function channel phenotype. Neuroscience, 2017, 351, 65-70.
[http://dx.doi.org/10.1016/j.neuroscience.2017.03.035] [PMID: 28366665]
[75]
Quraishi, I.H.; Mercier, M.R.; McClure, H.; Couture, R.L.; Schwartz, M.L.; Lukowski, R.; Ruth, P.; Kaczmarek, L.K. Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (KNa1.1) Na+-activated K+ channels. Sci. Rep., 2020, 10(1), 3213.
[http://dx.doi.org/10.1038/s41598-020-60028-z] [PMID: 32081855]
[76]
McTague, A.; Nair, U.; Malhotra, S.; Meyer, E.; Trump, N.; Gazina, E.V.; Papandreou, A.; Ngoh, A.; Ackermann, S.; Ambegaonkar, G.; Appleton, R.; Desurkar, A.; Eltze, C.; Kneen, R.; Kumar, A.V.; Lascelles, K.; Montgomery, T.; Ramesh, V.; Samanta, R.; Scott, R.H.; Tan, J.; Whitehouse, W.; Poduri, A.; Scheffer, I.E.; Chong, W.K.K.; Cross, J.H.; Topf, M.; Petrou, S.; Kurian, M.A. Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy. Neurology, 2018, 90(1), e55-e66.
[http://dx.doi.org/10.1212/WNL.0000000000004762] [PMID: 29196579]
[77]
Ishii, A.; Shioda, M.; Okumura, A.; Kidokoro, H.; Sakauchi, M.; Shimada, S.; Shimizu, T.; Osawa, M.; Hirose, S.; Yamamoto, T. A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy. Gene, 2013, 531(2), 467-471.
[http://dx.doi.org/10.1016/j.gene.2013.08.096] [PMID: 24029078]
[78]
Scheffer, I.E.; Jones, L.; Pozzebon, M.; Howell, R.A.; Saling, M.M.; Berkovic, S.F. Autosomal dominant rolandic epilepsy and speech dyspraxia: a new syndrome with anticipation. Ann. Neurol., 1995, 38(4), 633-642.
[http://dx.doi.org/10.1002/ana.410380412] [PMID: 7574460]
[79]
Tamsett, T.J.; Picchione, K.E.; Bhattacharjee, A. NAD+ activates KNa channels in dorsal root ganglion neurons. J. Neurosci., 2009, 29(16), 5127-5134.
[http://dx.doi.org/10.1523/JNEUROSCI.0859-09.2009] [PMID: 19386908]
[80]
Ramsey, K.M.; Yoshino, J.; Brace, C.S.; Abrassart, D.; Kobayashi, Y.; Marcheva, B.; Hong, H.K.; Chong, J.L.; Buhr, E.D.; Lee, C.; Takahashi, J.S.; Imai, S.; Bass, J. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science, 2009, 324(5927), 651-654.
[http://dx.doi.org/10.1126/science.1171641] [PMID: 19299583]
[81]
Pfeiffer, B.E.; Huber, K.M. The state of synapses in fragile X syndrome. Neuroscientist, 2009, 15(5), 549-567.
[http://dx.doi.org/10.1177/1073858409333075] [PMID: 19325170]
[82]
Bausch, A.E.; Dieter, R.; Nann, Y.; Hausmann, M.; Bausch, A.E.; Dieter, R.; Nann, Y.; Hausmann, M.; Meyerdierks, N.; Kaczmarek, L.K.; Ruth, P.; Lukowski, R. The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice. Learn. Mem., 2015, 22(7), 323-335.
[http://dx.doi.org/10.1101/lm.037820.114] [PMID: 26077685]
[83]
Bausch, A.E.; Ehinger, R.; Straubinger, J.; Zerfass, P.; Nann, Y.; Lukowski, R. Loss of sodium-activated potassium channel slack and FMRP differentially affect social behavior in mice. Neuroscience, 2018, 384, 361-374.
[http://dx.doi.org/10.1016/j.neuroscience.2018.05.040] [PMID: 29859980]
[84]
Musumeci, S.A.; Hagerman, R.J.; Ferri, R.; Bosco, P.; Dalla Bernardina, B.; Tassinari, C.A.; De Sarro, G.B.; Elia, M. Epilepsy and EEG findings in males with fragile X syndrome. Epilepsia, 1999, 40(8), 1092-1099.
[http://dx.doi.org/10.1111/j.1528-1157.1999.tb00824.x] [PMID: 10448821]
[85]
Sabaratnam, M.; Vroegop, P.G.; Gangadharan, S.K. Epilepsy and EEG findings in 18 males with fragile X syndrome. Seizure, 2001, 10(1), 60-63.
[http://dx.doi.org/10.1053/seiz.2000.0492] [PMID: 11181100]
[86]
Zemelman, B.V.; Lee, G.A.; Ng, M.; Miesenböck, G. Selective photostimulation of genetically chARGed neurons. Neuron, 2002, 33(1), 15-22.
[http://dx.doi.org/10.1016/S0896-6273(01)00574-8] [PMID: 11779476]
[87]
Li, X.; Gutierrez, D.V.; Hanson, M.G.; Han, J.; Mark, M.D.; Chiel, H.; Hegemann, P.; Landmesser, L.T.; Herlitze, S. Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc. Natl. Acad. Sci. USA, 2005, 102(49), 17816-17821.
[http://dx.doi.org/10.1073/pnas.0509030102] [PMID: 16306259]
[88]
Boyden, E.S.; Zhang, F.; Bamberg, E.; Nagel, G.; Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci., 2005, 8(9), 1263-1268.
[http://dx.doi.org/10.1038/nn1525] [PMID: 16116447]
[89]
Lu, Y.; Zhong, C.; Wang, L.; Wei, P.; He, W.; Huang, K.; Zhang, Y.; Zhan, Y.; Feng, G.; Wang, L. Optogenetic dissection of ictal propagation in the hippocampal-entorhinal cortex structures. Nat. Commun., 2016, 7, 10962.
[http://dx.doi.org/10.1038/ncomms10962] [PMID: 26997093]
[90]
Paz, J.T.; Davidson, T.J.; Frechette, E.S.; Delord, B.; Parada, I.; Peng, K.; Deisseroth, K.; Huguenard, J.R. Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury. Nat. Neurosci., 2013, 16(1), 64-70.
[http://dx.doi.org/10.1038/nn.3269] [PMID: 23143518]
[91]
Buzsáki, G. Large-scale recording of neuronal ensembles. Nat. Neurosci., 2004, 7(5), 446-451.
[http://dx.doi.org/10.1038/nn1233] [PMID: 15114356]
[92]
Merricks, E.M.; Smith, E.H.; McKhann, G.M.; Goodman, R.R.; Bateman, L.M.; Emerson, R.G.; Schevon, C.A.; Trevelyan, A.J. Single unit action potentials in humans and the effect of seizure activity. Brain, 2015, 138(Pt 10), 2891-2906.
[http://dx.doi.org/10.1093/brain/awv208] [PMID: 26187332]
[93]
Broussard, G.J.; Liang, R.; Tian, L. Monitoring activity in neural circuits with genetically encoded indicators. Front. Mol. Neurosci., 2014, 7, 97.
[http://dx.doi.org/10.3389/fnmol.2014.00097] [PMID: 25538558]
[94]
Suresh, N.T. ; e R, V.; U, K. Multi-scale top-down approach for modelling epileptic protein-protein interaction network analysis to identify driver nodes and pathways. Comput. Biol. Chem., 2020, 88, 107323.
[http://dx.doi.org/10.1016/j.compbiolchem.2020.107323] [PMID: 32653778]
[95]
Marsh, E.; Melamed, S.E.; Barron, T.; Clancy, R.R. Migrating partial seizures in infancy: expanding the phenotype of a rare seizure syndrome. Epilepsia, 2005, 46(4), 568-572.
[http://dx.doi.org/10.1111/j.0013-9580.2005.34104.x] [PMID: 15816952]
[96]
McTague, A.; Appleton, R.; Avula, S.; Cross, J.H.; King, M.D.; Jacques, T.S.; Bhate, S.; Cronin, A.; Curran, A.; Desurkar, A.; Farrell, M.A.; Hughes, E.; Jefferson, R.; Lascelles, K.; Livingston, J.; Meyer, E.; McLellan, A.; Poduri, A.; Scheffer, I.E.; Spinty, S.; Kurian, M.A.; Kneen, R. Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum. Brain, 2013, 136(Pt 5), 1578-1591.
[http://dx.doi.org/10.1093/brain/awt073] [PMID: 23599387]
[97]
Yang, B.; Gribkoff, V.K.; Pan, J.; Damagnez, V.; Dworetzky, S.I.; Boissard, C.G.; Bhattacharjee, A.; Yan, Y.; Sigworth, F.J.; Kaczmarek, L.K. Pharmacological activation and inhibition of Slack (Slo2.2) channels. Neuropharmacology, 2006, 51(4), 896-906.
[http://dx.doi.org/10.1016/j.neuropharm.2006.06.003] [PMID: 16876206]
[98]
Jia, Y.; Lin, Y.; Li, J.; Li, M.; Zhang, Y.; Hou, Y.; Liu, A.; Zhang, L.; Li, L.; Xiang, P.; Ye, J.; Huang, Z.; Wang, Y. Quinidine therapy for lennox-gastaut syndrome With KCNT1 mutation. A case report and literature review. Front. Neurol., 2019, 10, 64.
[http://dx.doi.org/10.3389/fneur.2019.00064] [PMID: 30804880]
[99]
Abdelnour, E.; Gallentine, W.; McDonald, M.; Sachdev, M.; Jiang, Y.H.; Mikati, M.A. Does age affect response to quinidine in patients with KCNT1 mutations? Report of three new cases and review of the literature. Seizure, 2018, 55, 1-3.
[http://dx.doi.org/10.1016/j.seizure.2017.11.017] [PMID: 29291456]
[100]
Bearden, D.; Strong, A.; Ehnot, J.; DiGiovine, M.; Dlugos, D.; Goldberg, E.M. Targeted treatment of migrating partial seizures of infancy with quinidine. Ann. Neurol., 2014, 76(3), 457-461.
[http://dx.doi.org/10.1002/ana.24229] [PMID: 25042079]
[101]
Dilena, R.; DiFrancesco, J.C.; Soldovieri, M.V.; Giacobbe, A.; Ambrosino, P.; Mosca, I.; Galli, M.A.; Guez, S.; Fumagalli, M.; Miceli, F.; Cattaneo, D.; Darra, F.; Gennaro, E.; Zara, F.; Striano, P.; Castellotti, B.; Gellera, C.; Varesio, C.; Veggiotti, P.; Taglialatela, M. Early treatment with quinidine in 2 patients with epilepsy of infancy with migrating focal seizures (EIMFS) due to gain-of-function KCNT1 mutations: functional studies, clinical responses, and critical issues for personalized therapy. Neurotherapeutics, 2018, 15(4), 1112-1126.
[http://dx.doi.org/10.1007/s13311-018-0657-9] [PMID: 30112700]
[102]
de Los Angeles Tejada, M.; Stolpe, K.; Meinild, A.K.; Klaerke, D.A. Clofilium inhibits slick and slack potassium channels. Biologics, 2012, 6, 465-470.
[http://dx.doi.org/10.2147/BTT.S33827] [PMID: 23271893]
[103]
Cole, B.A.; Clapcote, S.J.; Muench, S.P.; Lippiat, J.D. Targeting KNa1.1 channels in KCNT1-associated epilepsy. Trends Pharmacol. Sci., 2021, 42(8), 700-713.
[http://dx.doi.org/10.1016/j.tips.2021.05.003] [PMID: 34074526]
[104]
Cole, B.A.; Johnson, R.M.; Dejakaisaya, H.; Pilati, N.; Fishwick, C.W.G.; Muench, S.P.; Lippiat, J.D. Structure-based identification and characterization of inhibitors of the epilepsy-associated KNa1.1 (KCNT1) potassium channel. iScience 2020. 23(5), 101100.
[http://dx.doi.org/10.1016/j.isci.2020.101100] [PMID: 32408169]
[105]
Spitznagel, B.D.; Mishra, N.M.; Qunies, A.M.; Prael, F.J., III; Du, Y.; Kozek, K.A.; Lazarenko, R.M.; Denton, J.S.; Emmitte, K.A.; Weaver, C.D. VU0606170, a selective slack channels inhibitor, decreases calcium oscillations in cultured cortical neurons. ACS Chem. Neurosci., 2020, 11(21), 3658-3671.
[http://dx.doi.org/10.1021/acschemneuro.0c00583] [PMID: 33143429]
[106]
Griffin, A.M.; Kahlig, K.M.; Hatch, R.J.; Hughes, Z.A.; Chapman, M.L.; Antonio, B.; Marron, B.E.; Wittmann, M.; Martinez-Botella, G. Discovery of the first orally available, selective KNa1.1 inhibitor: in vitro and in vivo activity of an oxadiazole series. ACS Med. Chem. Lett., 2021, 12(4), 593-602.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00675] [PMID: 33859800]

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