Upregulated Connexin 43 Induced by Loss-of-Functional S284L-Mutant α4 Subunit of Nicotinic ACh Receptor Contributes to Pathomechanisms of Autosomal Dominant Sleep-Related Hypermotor Epilepsy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemical Agents
2.2. Preparation of the Microdialysis System
2.3. Experimental Designs of Microdialysis Study
2.3.1. Study_1: Effects of Subchronic Administration of the Therapeutic-Relevant Dose of ZNS on Glutamatergic Transmission in the Thalamocortical Motor Pathway
2.3.2. Study_2: Interaction between Subchronic Administration of the Therapeutic-Relevant Dose of ZNS and Acute Local Administration of GAP19 into the M2C on Glutamatergic Transmission in the Thalamocortical Motor Pathway
2.3.3. Study_3: Effects of Subchronic Administration of the Therapeutic-Relevant Dose of ZNS and Acute Local Administration of GAP19 into the M2C on Repetitive Potassium-Dependent L-Glutamate Release in the M2C
2.4. Ultra-High-Performance Liquid-Chromatography (UHPLC)
2.5. Preparation of Primary Astrocyte Culture
2.6. Simple Western Analysis
2.7. Data Analysis
2.8. Nomenclature of Targets and Ligands
3. Results
3.1. Cx43 Expression in the M2C Plasma Membrane Fraction of S286L-TG and Its Response to Subchronic Nicotine Administration In Vivo
3.2. Effects of Subchronic Administration of Nicotine and ZNS on Cx43 Expression in Astroglial Plasma Membrane Fractions of Wild-Type Primary Cultured Astrocytes
3.3. Effects of Subchronic Administration of Therapeutic-Relevant Dose of ZNS on Cx43 Expression in the M2C Plasma Membrane of Wild-Type and S286L-TG
3.4. Microdialysis Study
3.4.1. Effects of Local Administration of RJR2403 into the RTN and Subchronic Administration of Therapeutic-Relevant Dose of ZNS on the L-Glutamate Release in the M2C Induced by Local Administration of AMPA into the MoTN (Study_1)
3.4.2. Interaction between Local Administration of GAP19 into the M2C and the Subchronic Administration of Therapeutic-Relevant Dose of ZNS on AMPA-Evoked L-Glutamate Release in the M2C (Study_2)
3.5. Effects of Subchronic Administration of Therapeutic-Relevant Dose of ZNS on Repetitive Potassium-Evoked L-Glutamate Release in the M2C (Study_3-1)
3.6. Effects of Local Administration of GAP19 on Repetitive Potassium-Evoked L-Glutamate Release in the M2C (Study_3-2)
4. Discussion
4.1. Pathomechanism of ADSHE Seizures Associated with Cx43
4.2. Pathophysiology of ADSHE Seizures Associated with ZNS
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Steinlein, O.K. Animal models for autosomal dominant frontal lobe epilepsy: On the origin of seizures. Expert Rev. Neurother. 2010, 10, 1859–1867. [Google Scholar] [CrossRef]
- Tinuper, P.; Bisulli, F.; Cross, J.H.; Hesdorffer, D.; Kahane, P.; Nobili, L.; Provini, F.; Scheffer, I.E.; Tassi, L.; Vignatelli, L.; et al. Definition and diagnostic criteria of sleep-related hypermotor epilepsy. Neurology 2016, 86, 1834–1842. [Google Scholar] [CrossRef]
- Scheffer, I.E.; Bhatia, K.P.; Lopes-Cendes, I.; Fish, D.R.; Marsden, C.D.; Andermann, F.; Andermann, E.; Desbiens, R.; Cendes, F.; Manson, J.I.; et al. Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder. Lancet 1994, 343, 515–517. [Google Scholar] [CrossRef]
- Provini, F.; Plazzi, G.; Tinuper, P.; Vandi, S.; Lugaresi, E.; Montagna, P. Nocturnal frontal lobe epilepsy. A clinical and polygraphic overview of 100 consecutive cases. Brain 1999, 122 Pt 6, 1017–1031. [Google Scholar] [CrossRef] [Green Version]
- Okada, M.; Zhu, G.; Yoshida, S.; Kaneko, S. Validation criteria for genetic animal models of epilepsy. Epilepsy Seizure 2010, 3, 109–120. [Google Scholar] [CrossRef] [Green Version]
- Nobili, L.; Proserpio, P.; Combi, R.; Provini, F.; Plazzi, G.; Bisulli, F.; Tassi, L.; Tinuper, P. Nocturnal frontal lobe epilepsy. Curr. Neurol. Neurosci. Rep. 2014, 14, 424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Phillips, H.A.; Marini, C.; Scheffer, I.E.; Sutherland, G.R.; Mulley, J.C.; Berkovic, S.F. A de novo mutation in sporadic nocturnal frontal lobe epilepsy. Ann. Neurol. 2000, 48, 264–267. [Google Scholar] [CrossRef]
- Scheffer, I.E.; Bhatia, K.P.; Lopes-Cendes, I.; Fish, D.R.; Marsden, C.D.; Andermann, E.; Andermann, F.; Desbiens, R.; Keene, D.; Cendes, F.; et al. Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder. Brain 1995, 118 Pt 1, 61–73. [Google Scholar] [CrossRef] [Green Version]
- Provini, F.; Plazzi, G.; Montagna, P.; Lugaresi, E. The wide clinical spectrum of nocturnal frontal lobe epilepsy. Sleep Med. Rev. 2000, 4, 375–386. [Google Scholar] [CrossRef] [PubMed]
- Rozycka, A.; Skorupska, E.; Kostyrko, A.; Trzeciak, W.H. Evidence for S284L mutation of the CHRNA4 in a white family with autosomal dominant nocturnal frontal lobe epilepsy. Epilepsia 2003, 44, 1113–1117. [Google Scholar] [CrossRef]
- Ito, M.; Kobayashi, K.; Fujii, T.; Okuno, T.; Hirose, S.; Iwata, H.; Mitsudome, A.; Kaneko, S. Electroclinical picture of autosomal dominant nocturnal frontal lobe epilepsy in a Japanese family. Epilepsia 2000, 41, 52–58. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hirose, S.; Iwata, H.; Akiyoshi, H.; Kobayashi, K.; Ito, M.; Wada, K.; Kaneko, S.; Mitsudome, A. A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. Neurology 1999, 53, 1749–1753. [Google Scholar] [CrossRef] [PubMed]
- Miyajima, T.; Kumada, T.; Saito, K.; Fujii, T. Autism in siblings with autosomal dominant nocturnal frontal lobe epilepsy. Brain Dev. 2013, 35, 155–157. [Google Scholar] [CrossRef] [PubMed]
- Steinlein, O.K.; Mulley, J.C.; Propping, P.; Wallace, R.H.; Phillips, H.A.; Sutherland, G.R.; Scheffer, I.E.; Berkovic, S.F. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat. Genet. 1995, 11, 201–203. [Google Scholar] [CrossRef] [PubMed]
- Steinlein, O.K.; Stoodt, J.; Mulley, J.; Berkovic, S.; Scheffer, I.E.; Brodtkorb, E. Independent occurrence of the CHRNA4 Ser248Phe mutation in a Norwegian family with nocturnal frontal lobe epilepsy. Epilepsia 2000, 41, 529–535. [Google Scholar] [CrossRef] [Green Version]
- Magnusson, A.; Stordal, E.; Brodtkorb, E.; Steinlein, O. Schizophrenia, psychotic illness and other psychiatric symptoms in families with autosomal dominant nocturnal frontal lobe epilepsy caused by different mutations. Psychiatr. Genet. 2003, 13, 91–95. [Google Scholar] [CrossRef]
- Saenz, A.; Galan, J.; Caloustian, C.; Lorenzo, F.; Marquez, C.; Rodriguez, N.; Jimenez, M.D.; Poza, J.J.; Cobo, A.M.; Grid, D.; et al. Autosomal dominant nocturnal frontal lobe epilepsy in a Spanish family with a Ser252Phe mutation in the CHRNA4 gene. Arch. Neurol. 1999, 56, 1004–1009. [Google Scholar] [CrossRef] [Green Version]
- McLellan, A.; Phillips, H.A.; Rittey, C.; Kirkpatrick, M.; Mulley, J.C.; Goudie, D.; Stephenson, J.B.; Tolmie, J.; Scheffer, I.E.; Berkovic, S.F.; et al. Phenotypic comparison of two Scottish families with mutations in different genes causing autosomal dominant nocturnal frontal lobe epilepsy. Epilepsia 2003, 44, 613–617. [Google Scholar] [CrossRef] [Green Version]
- Cho, Y.W.; Motamedi, G.K.; Laufenberg, I.; Sohn, S.I.; Lim, J.G.; Lee, H.; Yi, S.D.; Lee, J.H.; Kim, D.K.; Reba, R.; et al. A Korean kindred with autosomal dominant nocturnal frontal lobe epilepsy and mental retardation. Arch. Neurol. 2003, 60, 1625–1632. [Google Scholar] [CrossRef]
- Steinlein, O.K.; Magnusson, A.; Stoodt, J.; Bertrand, S.; Weiland, S.; Berkovic, S.F.; Nakken, K.O.; Propping, P.; Bertrand, D. An insertion mutation of the CHRNA4 gene in a family with autosomal dominant nocturnal frontal lobe epilepsy. Hum. Mol. Genet. 1997, 6, 943–947. [Google Scholar] [CrossRef] [Green Version]
- Fukuyama, K.; Fukuzawa, M.; Shiroyama, T.; Okada, M. Pathogenesis and pathophysiology of autosomal dominant sleep-related hypermotor epilepsy with S284L-mutant alpha4 subunit of nicotinic ACh receptor. Br. J. Pharmacol. 2020. [Google Scholar] [CrossRef]
- Fukuyama, K.; Fukuzawa, M.; Shiroyama, T.; Okada, M. Pathomechanism of nocturnal paroxysmal dystonia in autosomal dominant sleep-related hypermotor epilepsy with S284L-mutant alpha4 subunit of nicotinic ACh receptor. Biomed. Pharmacother. 2020, 126, 110070. [Google Scholar] [CrossRef]
- Zhu, G.; Okada, M.; Yoshida, S.; Ueno, S.; Mori, F.; Takahara, T.; Saito, R.; Miura, Y.; Kishi, A.; Tomiyama, M.; et al. Rats harboring S284L Chrna4 mutation show attenuation of synaptic and extrasynaptic GABAergic transmission and exhibit the nocturnal frontal lobe epilepsy phenotype. J. Neurosci. 2008, 28, 12465–12476. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duerrschmidt, N.; Hagen, A.; Gaertner, C.; Wermke, A.; Nowicki, M.; Spanel-Borowski, K.; Stepan, H.; Mohr, F.W.; Dhein, S. Nicotine effects on human endothelial intercellular communication via alpha4beta2 and alpha3beta2 nicotinic acetylcholine receptor subtypes. Naunyn Schmiedebergs Arch. Pharmacol. 2012, 385, 621–632. [Google Scholar] [CrossRef]
- Medina-Ceja, L.; Salazar-Sanchez, J.C.; Ortega-Ibarra, J.; Morales-Villagran, A. Connexins-based hemichannels/channels and their relationship with inflammation, seizures and epilepsy. Int. J. Mol. Sci. 2019, 20, 5976. [Google Scholar] [CrossRef] [Green Version]
- Li, Q.; Li, Q.Q.; Jia, J.N.; Liu, Z.Q.; Zhou, H.H.; Mao, X.Y. Targeting gap junction in epilepsy: Perspectives and challenges. Biomed. Pharmacother. 2019, 109, 57–65. [Google Scholar] [CrossRef]
- Lapato, A.S.; Tiwari-Woodruff, S.K. Connexins and pannexins: At the junction of neuro-glial homeostasis & disease. J. Neurosci. Res. 2018, 96, 31–44. [Google Scholar] [PubMed]
- Ribeiro-Rodrigues, T.M.; Martins-Marques, T.; Morel, S.; Kwak, B.R.; Girao, H. Role of connexin 43 in different forms of intercellular communication—Gap junctions, extracellular vesicles and tunnelling nanotubes. J. Cell Sci. 2017, 130, 3619–3630. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dallerac, G.; Rouach, N. Astrocytes as new targets to improve cognitive functions. Prog. Neurobiol. 2016, 144, 48–67. [Google Scholar] [CrossRef] [PubMed]
- Mylvaganam, S.; Ramani, M.; Krawczyk, M.; Carlen, P.L. Roles of gap junctions, connexins, and pannexins in epilepsy. Front. Physiol. 2014, 5, 172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, X.M.; Wang, G.L.; Miao, J.; Feng, J.C. Effect of connexin 36 blockers on the neuronal cytoskeleton and synaptic plasticity in kainic acid-kindled rats. Transl. Neurosci. 2015, 6, 252–258. [Google Scholar] [CrossRef] [PubMed]
- Jin, M.; Dai, Y.; Xu, C.; Wang, Y.; Wang, S.; Chen, Z. Effects of meclofenamic acid on limbic epileptogenesis in mice kindling models. Neurosci. Lett. 2013, 543, 110–114. [Google Scholar] [CrossRef] [PubMed]
- Fukuyama, K.; Okubo, R.; Murata, M.; Shiroyama, T.; Okada, M. Activation of astroglial connexin is involved in concentration-dependent double-edged sword clinical action of clozapine. Cells 2020, 9, 414. [Google Scholar] [CrossRef] [Green Version]
- Fukuyama, K.; Kato, R.; Murata, M.; Shiroyama, T.; Okada, M. Clozapine normalizes a glutamatergic transmission abnormality induced by an impaired NMDA receptor in the thalamocortical pathway via the activation of a group III metabotropic glutamate receptor. Biomolecules 2019, 9, 234. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alexander, S.P.H.; Mathie, A.; Peters, J.A.; Veale, E.L.; Striessnig, J.; Kelly, E.; Armstrong, J.F.; Faccenda, E.; Harding, S.D.; Pawson, A.J.; et al. The concise guide to pharmacology 2019/20: Ion channels. Br. J. Pharmacol. 2019, 176 (Suppl. 1), S142–S228. [Google Scholar] [CrossRef] [Green Version]
- Wang, N.; De Bock, M.; Decrock, E.; Bol, M.; Gadicherla, A.; Bultynck, G.; Leybaert, L. Connexin targeting peptides as inhibitors of voltage- and intracellular Ca2+-triggered Cx43 hemichannel opening. Neuropharmacology 2013, 75, 506–516. [Google Scholar] [CrossRef]
- Yamamura, S.; Saito, H.; Suzuki, N.; Kashimoto, S.; Hamaguchi, T.; Ohoyama, K.; Suzuki, D.; Kanehara, S.; Nakagawa, M.; Shiroyama, T.; et al. Effects of zonisamide on neurotransmitter release associated with inositol triphosphate receptors. Neurosci. Lett. 2009, 454, 91–96. [Google Scholar] [CrossRef]
- Yoshida, S.; Okada, M.; Zhu, G.; Kaneko, S. Effects of zonisamide on neurotransmitter exocytosis associated with ryanodine receptors. Epilepsy Res. 2005, 67, 153–162. [Google Scholar] [CrossRef]
- Okada, M.; Zhu, G.; Yoshida, S.; Kanai, K.; Hirose, S.; Kaneko, S. Exocytosis mechanism as a new targeting site for mechanisms of action of antiepileptic drugs. Life Sci. 2002, 72, 465–473. [Google Scholar] [CrossRef]
- Yamamura, S.; Ohoyama, K.; Nagase, H.; Okada, M. Zonisamide enhances delta receptor-associated neurotransmitter release in striato-pallidal pathway. Neuropharmacology 2009, 57, 322–331. [Google Scholar] [CrossRef]
- Benowitz, N.L.; Chan, K.; Denaro, C.P.; Jacob, P., 3rd. Stable isotope method for studying transdermal drug absorption: The nicotine patch. Clin. Pharmacol. Ther. 1991, 50, 286–293. [Google Scholar] [CrossRef] [PubMed]
- McGrath, J.C.; Lilley, E. Implementing guidelines on reporting research using animals (ARRIVE etc.): New requirements for publication in BJP. Br. J. Pharmacol. 2015, 172, 3189–3193. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Paxinos, G.; Watson, C. The Rat Brain: In Stereotoxic Coordinates, 6th ed.; Academic Press: San Dieg, CA, USA, 2007. [Google Scholar]
- Zhu, G.; Okada, M.; Murakami, T.; Kawata, Y.; Kamata, A.; Kaneko, S. Interaction between carbamazepine, zonisamide and voltage-sensitive Ca2+ channel on acetylcholine release in rat frontal cortex. Epilepsy Res. 2002, 49, 49–60. [Google Scholar] [CrossRef]
- Mtui, E.; Gruener, G.; Dockery, P. Fitzgerald’s Clinical Neuroanatomy and Neuroscience, 7th ed.; Elsevier: Amsterdam, The Netherlands, 2015. [Google Scholar]
- Karlsen, A.S.; Korbo, S.; Uylings, H.B.; Pakkenberg, B. A stereological study of the mediodorsal thalamic nucleus in Down syndrome. Neuroscience 2014, 279, 253–259. [Google Scholar] [CrossRef] [PubMed]
- Yamamura, S.; Hoshikawa, M.; Dai, K.; Saito, H.; Suzuki, N.; Niwa, O.; Okada, M. ONO-2506 inhibits spike-wave discharges in a genetic animal model without affecting traditional convulsive tests via gliotransmission regulation. Br. J. Pharmacol. 2013, 168, 1088–1100. [Google Scholar] [CrossRef] [PubMed]
- Fukuyama, K.; Tanahashi, S.; Hoshikawa, M.; Shinagawa, R.; Okada, M. Zonisamide regulates basal ganglia transmission via astroglial kynurenine pathway. Neuropharmacology 2014, 76 Pt A, 137–145. [Google Scholar] [CrossRef]
- Okada, M.; Fukuyama, K.; Shiroyama, T.; Ueda, Y. Carbamazepine attenuates astroglial l-glutamate release induced by pro-inflammatory cytokines via chronically activation of adenosine A2A receptor. Int. J. Mol. Sci. 2019, 20, 3727. [Google Scholar] [CrossRef] [Green Version]
- Okada, M.; Fukuyama, K.; Shiroyama, T.; Ueda, Y. Lurasidone inhibits NMDA antagonist-induced functional abnormality of thalamocortical glutamatergic transmission via 5-HT7 receptor blockade. Br. J. Pharmacol. 2019, 176, 4002–4018. [Google Scholar] [CrossRef]
- Okada, M.; Fukuyama, K.; Kawano, Y.; Shiroyama, T.; Ueda, Y. Memantine protects thalamocortical hyper-glutamatergic transmission induced by NMDA receptor antagonism via activation of system xc−. Pharmacol. Res. Perspect. 2019, 7, e00457. [Google Scholar] [CrossRef] [Green Version]
- Okada, M.; Fukuyama, K.; Kawano, Y.; Shiroyama, T.; Suzuki, D.; Ueda, Y. Effects of acute and sub-chronic administrations of guanfacine on catecholaminergic transmissions in the orbitofrontal cortex. Neuropharmacology 2019, 156, 107547. [Google Scholar] [CrossRef]
- Curtis, M.J.; Alexander, S.; Cirino, G.; Docherty, J.R.; George, C.H.; Giembycz, M.A.; Hoyer, D.; Insel, P.A.; Izzo, A.A.; Ji, Y.; et al. Experimental design and analysis and their reporting II: Updated and simplified guidance for authors and peer reviewers. Br. J. Pharmacol. 2018, 175, 987–993. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harding, S.D.; Sharman, J.L.; Faccenda, E.; Southan, C.; Pawson, A.J.; Ireland, S.; Gray, A.J.G.; Bruce, L.; Alexander, S.P.H.; Anderton, S.; et al. The IUPHAR/BPS Guide to pharmacology in 2018: Updates and expansion to encompass the new guide to immunopharmacology. Nucleic Acids Res. 2018, 46, D1091–D1106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alexander, S.P.H.; Christopoulos, A.; Davenport, A.P.; Kelly, E.; Mathie, A.; Peters, J.A.; Veale, E.L.; Armstrong, J.F.; Faccenda, E.; Harding, S.D.; et al. The concise guide to pharmacology 2019/20: G protein-coupled receptors. Br. J. Pharmacol. 2019, 176 (Suppl. 1), S21–S141. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodrigues-Pinguet, N.; Jia, L.; Li, M.; Figl, A.; Klaassen, A.; Truong, A.; Lester, H.A.; Cohen, B.N. Five ADNFLE mutations reduce the Ca2+ dependence of the mammalian alpha4beta2 acetylcholine response. J. Physiol. 2003, 550, 11–26. [Google Scholar] [CrossRef]
- Rodrigues-Pinguet, N.O.; Pinguet, T.J.; Figl, A.; Lester, H.A.; Cohen, B.N. Mutations linked to autosomal dominant nocturnal frontal lobe epilepsy affect allosteric Ca2+ activation of the alpha 4 beta 2 nicotinic acetylcholine receptor. Mol. Pharmacol. 2005, 68, 487–501. [Google Scholar] [CrossRef] [Green Version]
- Kawata, Y.; Okada, M.; Murakami, T.; Mizuno, K.; Wada, K.; Kondo, T.; Kaneko, S. Effects of zonisamide on K+ and Ca2+ evoked release of monoamine as well as K+ evoked intracellular Ca2+ mobilization in rat hippocampus. Epilepsy Res. 1999, 35, 173–182. [Google Scholar] [CrossRef]
- Fukuyama, K.; Okada, M. Effects of levetiracetam on astroglial release of kynurenine-pathway metabolites. Br. J. Pharmacol. 2018, 175, 4253–4265. [Google Scholar] [CrossRef] [Green Version]
- Garbelli, R.; Frassoni, C.; Condorelli, D.F.; Trovato Salinaro, A.; Musso, N.; Medici, V.; Tassi, L.; Bentivoglio, M.; Spreafico, R. Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex. Neurology 2011, 76, 895–902. [Google Scholar] [CrossRef]
- Das, A.; Wallace, G.C.T.; Holmes, C.; McDowell, M.L.; Smith, J.A.; Marshall, J.D.; Bonilha, L.; Edwards, J.C.; Glazier, S.S.; Ray, S.K.; et al. Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors. Neuroscience 2012, 220, 237–246. [Google Scholar] [CrossRef] [Green Version]
- Yamamura, S.; Hamaguchi, T.; Ohoyama, K.; Sugiura, Y.; Suzuki, D.; Kanehara, S.; Nakagawa, M.; Motomura, E.; Matsumoto, T.; Tanii, H.; et al. Topiramate and zonisamide prevent paradoxical intoxication induced by carbamazepine and phenytoin. Epilepsy Res. 2009, 84, 172–186. [Google Scholar] [CrossRef]
- Flores, C.E.; Nannapaneni, S.; Davidson, K.G.; Yasumura, T.; Bennett, M.V.; Rash, J.E.; Pereda, A.E. Trafficking of gap junction channels at a vertebrate electrical synapse in vivo. Proc. Natl. Acad. Sci. USA 2012, 109, E573–E582. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pinault, D. The thalamic reticular nucleus: Structure, function and concept. Brain Res. Rev. 2004, 46, 1–31. [Google Scholar] [CrossRef] [PubMed]
- Suzuki-Yagawa, Y.; Kawakami, K.; Nagano, K. Housekeeping Na,K-ATPase alpha 1 subunit gene promoter is composed of multiple cis elements to which common and cell type-specific factors bind. Mol. Cell. Biol. 1992, 12, 4046–4055. [Google Scholar] [CrossRef] [Green Version]
- Mizuno, K.; Okada, M.; Murakami, T.; Kamata, A.; Zhu, G.; Kawata, Y.; Wada, K.; Kaneko, S. Effects of carbamazepine on acetylcholine release and metabolism. Epilepsy Res. 2000, 40, 187–195. [Google Scholar] [CrossRef]
- Omura, T.; Kaneko, M.; Okuma, Y.; Matsubara, K.; Nomura, Y. Endoplasmic reticulum stress and Parkinson’s disease: The role of HRD1 in averting apoptosis in neurodegenerative disease. Oxidative Med. Cell. Longev. 2013, 2013, 239854. [Google Scholar] [CrossRef]
- Steinhauser, C.; Seifert, G.; Bedner, P. Astrocyte dysfunction in temporal lobe epilepsy: K+ channels and gap junction coupling. Glia 2012, 60, 1192–1202. [Google Scholar] [CrossRef]
- Ek Vitorin, J.F.; Pontifex, T.K.; Burt, J.M. Determinants of Cx43 channel gating and permeation: The amino terminus. Biophys. J. 2016, 110, 127–140. [Google Scholar] [CrossRef] [Green Version]
- Okada, M.; Kaneko, S. Different mechanisms underlying the antiepileptic and antiparkinsonian effects of zonisamide. In Novel Treatment of Epilepsy; Foyaca-Sibat, H., Ed.; InTech: Rijeka, Croatia, 2011; pp. 23–36. [Google Scholar]
- Okada, M.; Kawata, Y.; Mizuno, K.; Wada, K.; Kondo, T.; Kaneko, S. Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode. Br. J. Pharmacol. 1998, 124, 1277–1285. [Google Scholar] [CrossRef] [Green Version]
- Okada, M.; Kaneko, S.; Hirano, T.; Mizuno, K.; Kondo, T.; Otani, K.; Fukushima, Y. Effects of zonisamide on dopaminergic system. Epilepsy Res. 1995, 22, 193–205. [Google Scholar] [CrossRef]
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Fukuyama, K.; Fukuzawa, M.; Okubo, R.; Okada, M. Upregulated Connexin 43 Induced by Loss-of-Functional S284L-Mutant α4 Subunit of Nicotinic ACh Receptor Contributes to Pathomechanisms of Autosomal Dominant Sleep-Related Hypermotor Epilepsy. Pharmaceuticals 2020, 13, 58. https://doi.org/10.3390/ph13040058
Fukuyama K, Fukuzawa M, Okubo R, Okada M. Upregulated Connexin 43 Induced by Loss-of-Functional S284L-Mutant α4 Subunit of Nicotinic ACh Receptor Contributes to Pathomechanisms of Autosomal Dominant Sleep-Related Hypermotor Epilepsy. Pharmaceuticals. 2020; 13(4):58. https://doi.org/10.3390/ph13040058
Chicago/Turabian StyleFukuyama, Kouji, Masashi Fukuzawa, Ruri Okubo, and Motohiro Okada. 2020. "Upregulated Connexin 43 Induced by Loss-of-Functional S284L-Mutant α4 Subunit of Nicotinic ACh Receptor Contributes to Pathomechanisms of Autosomal Dominant Sleep-Related Hypermotor Epilepsy" Pharmaceuticals 13, no. 4: 58. https://doi.org/10.3390/ph13040058