ArticleHuman molecular genetics2017
Scn2a deletion improves survival and brain-heart dynamics in the Kcna1-null mouse model of sudden unexpected death in epilepsy (SUDEP).
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 62 citations in OpenAlex.
- Sex-specific differences in mortality and neurocardiac interactions in the Kv1.1 knockout mouse model of sudden unexpected death in epilepsy (SUDEP).The Journal of physiology · 2026Article
- Nonsense-mediated decay influences position-dependent effects of SCN2A premature stop codons on neuronal excitability and behavior.Molecular psychiatry · 2026Article
- Cardiac-specific Kv1.1 deficiency alters cardiomyocyte electrophysiology without modifying overall cardiac function or arrhythmia susceptibility.Experimental physiology · 2026Article
- Review
- The Crucial Interplay Between the Lungs, Brain, and Heart to Understand Epilepsy-Linked SUDEP: A Literature Review.Brain sciences · 2025Review
- DecipheringArXiv · 2024Article
- Voltage-Gated Ion Channel Compensatory Effect in DEE: Implications for Future Therapies.Cells · 2024Review
- Epilepsy-associated Kv1.1 channel subunits regulate intrinsic cardiac pacemaking in mice.The Journal of general physiology · 2024Article
- Challenges and future directions of SUDEP models.Lab animal · 2024Review
- Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites.Neuron · 2024Article
- Strain-dependent effects on neurobehavioral and seizure phenotypes inbioRxiv : the preprint server for biology · 2023Article
- Novel Genetic Variants Expand the Functional, Molecular, and Pathological Diversity ofInternational journal of molecular sciences · 2023Review
- Article
- Cellular and behavioral effects of altered NaV1.2 sodium channel ion permeability in Scn2aK1422E mice.Human molecular genetics · 2022Article
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
- Paradoxical hyperexcitability from NaCell reports · 2021Article
- Kv1.1 deficiency alters repetitive and social behaviors in mice and rescues autistic-like behaviors due to Scn2a haploinsufficiency.Brain and behavior · 2021Article
- Sodium channelopathies in neurodevelopmental disorders.Nature reviews. Neuroscience · 2021Review
- Kv1.1 potassium channel subunit deficiency alters ventricular arrhythmia susceptibility, contractility, and repolarization.Physiological reports · 2021Article
- Clinical Spectrum ofInternational journal of molecular sciences · 2020Review
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9 authors at 2 institutions in 1 country.
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Abstract
People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings. The human epilepsy gene Kcna1 encodes voltage-gated Kv1.1 potassium channels that act to dampen neuronal excitability whereas Scn2a encodes voltage-gated Nav1.2 sodium channels important for action potential initiation and conduction. SUDEP-prone Kcna1-/- mice with partial genetic ablation of Nav1.2 channels (i.e. Scn2a+/-; Kcna1-/-) exhibited a two-fold increase in survival. Classical analysis of EEG and ECG recordings separately showed significantly decreased seizure durations in Scn2a+/-; Kcna1-/- mice compared with Kcna1-/- mice, without substantial modification of cardiac abnormalities. Novel analysis of the EEG and ECG together revealed a significant reduction in EEG-ECG association in Kcna1-/- mice compared with wild types, which was partially restored in Scn2a+/-; Kcna1-/- mice. The degree of EEG-ECG association was also proportional to the survival rate of mice across genotypes. These results show that Scn2a gene deletion acts as protective genetic modifier of SUDEP and suggest measures of brain-heart association as potential indices of SUDEP susceptibility.
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