The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Specific deletion of Na V 1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome
Open accessAbstract
Heterozygous loss-of-function mutations in the brain sodium channel Na V 1.1 cause Dravet syndrome (DS), a pharmacoresistant infantile-onset epilepsy syndrome with comorbidities of cognitive impairment and premature death. Previous studies using a mouse model of DS revealed reduced sodium currents and impaired excitability in GABAergic interneurons in the hippocampus, leading to the hypothesis that impaired excitability of GABAergic inhibitory neurons is the cause of epilepsy and premature death in DS. However, other classes of GABAergic interneurons are less impaired, so the direct cause of hyperexcitability, epilepsy, and premature death has remained unresolved. We generated a floxed Scn1a mouse line and used the Cre-Lox method driven by an enhancer from the Dlx 1,2 locus for conditional deletion of Scn1a in forebrain GABAergic neurons. Immunocytochemical studies demonstrated selective loss of Na V 1.1 channels in GABAergic interneurons in cerebral cortex and hippocampus. Mice with this deletion died prematurely following generalized tonic-clonic seizures, and they were equally susceptible to thermal induction of seizures as mice with global deletion of Scn1a . Evidently, loss of Na V 1.1 channels in forebrain GABAergic neurons is both necessary and sufficient to cause epilepsy and premature death in DS.
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“DS occurs from loss of function of SCN1A, which encodes the α-subunit of the voltage-gated sodium channel NaV1.1, prominently expressed in the soma and axon initial segment of neurons (Cheah et al., 2012).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Cheah et al., 2012
In the citing paper
“In mouse models of Dravets syndrome cortical interneurons cannot sustain high-frequency firing, leading to circuit disinhibition, seizures, and premature death (194, 852).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [194]
In the citing paper
“Haploinsufficiency or pathogenic variants of Scn1a cause Dravet Syndrome, a common and intractable form of epileptic encephalopathy characterized by the early onset of seizures17–19.”
From Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans (2020) · cites this paper as [17]
In the citing paper
“As loss of expression of Scn1a is especially associated with PV cIN disfunction15–19”
From Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans (2020) · cites this paper as [17]
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Cites
Modification of seizure activity by electrical stimulation: II. Motor seizure
Racine, R. J. (1972) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(72)90177-0 · Cited by 7,141
From Ionic Currents to Molecular Mechanisms
Catterall, W. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)81133-2 · Cited by 2,124
Self-citationDe Novo Mutations in the Sodium-Channel Gene SCN1A Cause Severe Myoclonic Epilepsy of Infancy
Claes, L., Del-Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., & De Jonghe, P. (2001) · The American Journal of Human Genetics · doi:10.1086/320609 · Cited by 1,292
Yu, F. H., Mantegazza, M., Westenbroek, R. E., Robbins, C. A., Kalume, F., Burton, K. A., Spain, W. J., McKnight, G. S., Scheuer, T., & Catterall, W. A. (2006) · Nature Neuroscience · doi:10.1038/nn1754 · Cited by 1,173
Self-citationThe origin and specification of cortical interneurons
Wonders, C. P., & Anderson, S. A. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1954 · Cited by 980 · cited 2×
“To target gene expression in GABAergic neurons selectively, we have taken advantage of the Dlx gene family, which encodes homeobox transcription factors that are required for specification, maturation, and survival of forebrain GABAergic neurons (20, 21).”
BackgroundOgiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5270-06.2007 · Cited by 879
The core Dravet syndrome phenotype
Dravet, C. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.02994.x · Cited by 630
Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy
Cobos, I., Calcagnotto, M. E., Vilaythong, A. J., Thwin, M. T., Noebels, J. L., Baraban, S. C., & Rubenstein, J. L. R. (2005) · Nature Neuroscience · doi:10.1038/nn1499 · Cited by 502
Self-citationThe VGL-Chanome: A Protein Superfamily Specialized for Electrical Signaling and Ionic Homeostasis
Yu, F. H., & Catterall, W. A. (2004) · Science s STKE · doi:10.1126/stke.2532004re15 · Cited by 488
Self-citationDifferential subcellular localization of the RI and RII Na+ channel subtypes in central neurons
Westenbroek, R. E., Merrick, D., & Catterall, W. A. (1989) · Neuron · doi:10.1016/0896-6273(89)90238-9 · Cited by 477
Self-citationLocalization of Voltage-Gated Ion Channels IN Mammalian Brain
Trimmer, J. S., & Rhodes, K. J. (2004) · Annual Review of Physiology · doi:10.1146/annurev.physiol.66.032102.113328 · Cited by 442
Catterall, W. A., Kalume, F., & Oakley, J. C. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.187484 · Cited by 428 · cited 1×
“1 channels cause multiple types of epilepsy (8, 9).”
BackgroundSelf-citationLocalization of Ca2+ Channel Subtypes on Rat Spinal Motor Neurons, Interneurons, and Nerve Terminals
Westenbroek, R., Hoskins, L., & Catterall, W. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-16-06319.1998 · Cited by 396
Self-citationSodium Channel β Subunits: Anything but Auxiliary
Isom, L. L. (2001) · The Neuroscientist · doi:10.1177/107385840100700108 · Cited by 354
Maier, S. K. G., Westenbroek, R. E., Schenkman, K. A., Feigl, E. O., Scheuer, T., & Catterall, W. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261705699 · Cited by 304
Self-citationDravet syndrome: The long‐term outcome
Genton, P., Velizarova, R., & Dravet, C. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03001.x · Cited by 266
Kalume, F. K., Yu, F. H., Westenbroek, R. E., Scheuer, T., & Catterall, W. A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2162-07.2007 · Cited by 262
Self-citationInherited Neuronal Ion Channelopathies: New Windows on Complex Neurological Diseases
Catterall, W. A., Dib-Hajj, S., Meisler, M. H., & Pietrobon, D. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3901-08.2008 · Cited by 237
Self-citationTemperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy
Oakley, J. C., Kalume, F. K., Yu, F. H., Scheuer, T., & Catterall, W. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813330106 · Cited by 237
Self-citationSodium channel gene family: epilepsy mutations, gene interactions and modifier effects
Meisler, M. H., O’Brien, J. E., & Sharkey, L. M. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.188482 · Cited by 215
Maier, S. K. G., Westenbroek, R. E., Yamanushi, T. T., Dobrzynski, H., Boyett, M. R., Catterall, W. A., & Scheuer, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2627986100 · Cited by 205
Self-citationLong, J. E., Swan, C. H., Liang, W. S., Cobos, I., Potter, G. B., & Rubenstein, J. L. R. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21854 · Cited by 156
Self-citationOguni, H., Hayashi, K., Awaya, Y., Fukuyama, Y., & Ōsawa, M. (2001) · Brain and Development · doi:10.1016/s0387-7604(01)00276-5 · Cited by 151
Potter, G. B., Petryniak, M. A., Shevchenko, E., McKinsey, G. L., Ekker, M., & Rubenstein, J. L. R. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.10.003 · Cited by 122
Self-citationNav1.1 channels with mutations of severe myoclonic epilepsy in infancy display attenuated currents
Sugawara, T., Tsurubuchi, Y., Fujiwara, T., Mazaki-Miyazaki, E., Nagata, K., Montal, M., Inoue, Y., & Yamakawa, K. (2003) · Epilepsy Research · doi:10.1016/s0920-1211(03)00084-6 · Cited by 79
Mortality in Dravet syndrome: Search for risk factors in Japanese patients
Sakauchi, M., Oguni, H., Kato, I., Ōsawa, M., Hirose, S., Kaneko, S., Takahashi, Y., Takayama, R., & Fujiwara, T. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03002.x · Cited by 74
Pure haploinsufficiency for Dravet syndrome NaV1.1 (SCN1A) sodium channel truncating mutations
Bechi, G., Scalmani, P., Schiavon, E., Rusconi, R., Franceschetti, S., & Mantegazza, M. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03346.x · Cited by 67
Broca's region revisited: Cytoarchitecture and intersubject variability
Amunts, K., Schleicher, A., B�rgel, U., Mohlberg, H., Uylings, H. B. M., & Zilles, K. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990920)412:2
Research works printed but not linked: 2
- F Kalume, JC Oakley, RE Westenbroek, T Scheuer, WA Catterall, Reduced excitability of GABAergic interneurons in the reticular nucleus of the thalamus and sleep impairment in a mouse model of Severe Myoclonic Epilepsy of Infancy. Soc Neurosci Abs 255, 15 (2010).
- Y Abe, F Kalume, RE Westenbroek, T Scheuer, WA Catterall, Effect of deletion of Nav1.1 channels on sodium current in dissociated neocortical interneurons in a mouse model of severe myoclonic epilepsy in infancy. Soc Neurosci Abs 254, 5 (2010).
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Hu, H., Gan, J., & Jonas, P. (2014) · Science · doi:10.1126/science.1255263 · Cited by 1,197
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders
Mariani, J., Coppola, G., Zhang, P., Abyzov, A., Provini, L., Tomasini, L., Amenduni, M., Szekely, A., Palejev, D., Wilson, M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.034 · Cited by 1,149
Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders
Nelson, S. B., & Valakh, V. (2015) · Neuron · doi:10.1016/j.neuron.2015.07.033 · Cited by 1,001
Hippocampal GABAergic Inhibitory Interneurons
Pelkey, K. A., Chittajallu, R., Craig, M. T., Tricoire, L., Wester, J. C., & McBain, C. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00007.2017 · Cited by 889
Autistic-like behaviour in Scn1a+/− mice and rescue by enhanced GABA-mediated neurotransmission
Han, S., Tai, C., Westenbroek, R. E., Yu, F. H., Cheah, C. S., Potter, G. B., Rubenstein, J. L., Scheuer, T., de la Iglesia, H. O., & Catterall, W. A. (2012) · Nature · doi:10.1038/nature11356 · Cited by 643
Self-citation
Metadata
- Authors
- Cheah, C. S., Yu, F. H., Westenbroek, R. E., Kalume, F. K., Oakley, J. C., Potter, G. B., Rubenstein, J. L., & Catterall, W. A.
- Affiliations
- Department of Pharmacology and
- Seoul National University (KR)
- University of Washington (US)
- University of California, San Francisco (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-08-20
- Volume
- 109
- Issue
- 36
- Pages
- 14646-14651
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3437823
- OpenAlex
- W2159213224
- Cited by
- 336
- References
- 28
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 32 · 2023: 26 · 2022: 23 · 2021: 42 · 2020: 21 · 2019: 28 · 2018: 16 · 2017: 19 · 2016: 24 · 2015: 20 · 2014: 21 · 2013: 23 · 2012: 1
- FWCI
- 14.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- McKnight Foundation
- National Research Foundation
- National Research Foundation of Korea
- National Institutes of Health (MH049428)
- National Institute of Mental Health (R37MH049428)
- National Institute of Neurological Disorders and Stroke (R01NS025704)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Dravet syndrome, Nav1.1 sodium channel, SCN1A, GABAergic interneurons, conditional knockout, epilepsy, premature mortality, seizures, hippocampus, cerebral cortex, tonic-clonic seizures
- MeSH terms
- Animals, Electrocardiography, Electroencephalography, Epilepsies, Myoclonic, Hippocampus, Immunohistochemistry, Interneurons, Mice, Transgenic, Mutation, Plasmids, Prosencephalon, Mice, NAV1.1 Voltage-Gated Sodium Channel
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