Dravet syndrome: a sodium channel interneuronopathy
Open accessAbstract
Dravet Syndrome is a devastating childhood epilepsy disorder with high incidence of premature death plus comorbidities of ataxia, circadian rhythm disorder, impaired sleep quality, autistic-like social-interaction deficits and severe cognitive impairment. It is primarily caused by heterozygous loss-of-function mutations in the SCN1A gene that encodes brain voltage-gated sodium channel type-1, termed Na V 1.1. Here I review experiments on mouse genetic models that implicate specific loss of sodium currents and action potential firing in GABAergic inhibitory interneurons as the fundamental cause of Dravet Syndrome. The resulting imbalance of excitatory to inhibitory neurotransmission in neural circuits causes both epilepsy and co-morbidities. Promising therapeutic approaches involving atypical sodium channel blockers, novel drug combinations, and cannabidiol give hope for improved outcomes for Dravet Syndrome patients.
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Loss of excitatory currents due to mutations in NaV1.1 (Scn1a) in Dravet Syndrome results in epilepsy.
“For example, loss of excitatory currents due to mutations in NaV1.1 (Scn1a) in Dravet Syndrome results in epilepsy.”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [38]
The Abstract attributes Dravet syndrome to loss of sodium currents and firing in GABAergic inhibitory interneurons, not to loss of excitatory currents. The Mouse Genetic Models section says excitatory neurotransmission increases in response to reduced inhibition. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredIn Dravet Syndrome, loss of excitatory to inhibitory synaptic neurotransmission leads to epilepsy.
“This was observed in the pathophysiology of Dravet Syndrome where a loss of excitatory to inhibitory synaptic neurotransmission leads to epilepsy [38, 73].”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [38]
The Mouse Genetic Models section reports reduced inhibitory GABAergic neurotransmission but increased excitatory neurotransmission; the Conclusion says the resulting imbalance leads to epilepsy. The paper therefore supports an excitation–inhibition imbalance as the cause, not a loss of excitatory-to-inhibitory synaptic neurotransmission as stated. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGenetic mouse models of Dravet Syndrome demonstrate that NaV1.1 loss predominantly impacts inhibitory circuitry leading to hyperexcitability.
“genetic mouse models of Dravet Syndrome demonstrate that NaV1.1 loss predominantly impacts inhibitory circuitry leading to hyperexcitability [38].”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [38]
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- Authors
- Catterall, W. A.
- Affiliations
- University of Washington (US)
- Corresponding author
- Catterall, William A
- ORCID
- Catterall, William A
- Venue
- Current Opinion in Physiology
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 2
- Pages
- 42-50
- ISSN
- 2468-8673 (ISSN-L)
- PMC
- PMC6091224
- OpenAlex
- W2513406030
- Cited by
- 148
- References
- 12
- Citations by year
- 2026: 18 · 2025: 11 · 2024: 20 · 2023: 24 · 2022: 18 · 2021: 29 · 2020: 12 · 2019: 15 · 2018: 1
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Opinion in Physiology (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 25470)
- Simons Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › 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, SCN1A, Nav1.1, voltage-gated sodium channels, GABAergic interneurons, loss-of-function mutations, pediatric epilepsy, excitatory-inhibitory imbalance, mouse model, cannabidiol, ataxia, circadian rhythm disorders, cognitive impairment
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