Unraveling Dravet Syndrome: Exploring the complex effects of sodium channel mutations on neuronal networks

Nina Doorn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Dravet Syndrome (DS) is a severe developmental epileptic encephalopathy with frequent intractable seizures accompanied by cognitive impairment, often caused by pathogenic variants in SCN1A encoding sodium channel NaV1.1. Recent research utilizing in vitro patient-derived neuronal networks and accompanying in silico models uncovered that not just sodium—but also potassium—and synaptic currents were impaired in DS networks. Here, we explore the implications of these findings for three questions that remain elusive in DS: How do sodium channel impairments result in epilepsy? How can identical variants lead to varying phenotypes? What mechanisms underlie the developmental delay in DS patients? We speculate that impaired potassium currents might be a secondary effect to NaV1.1 mutations and could result in hyperexcitable neurons and epileptic networks. Moreover, we reason that homeostatic plasticity is actively engaged in DS networks, possibly affecting the phenotype and impairing learning and development when driven to extremes.
Original languageEnglish
JournalScience Progress
Volume107
Issue number1
DOIs
Publication statusPublished - Jan 2024

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