학술논문
Cardiac-Specific Deletion of Scn8aMitigates Dravet Syndrome-Associated Sudden Death in Adults
Document Type
Article
Author
King, D. Ryan; Demirtas, Mustafa; Tarasov, Mikhail; Struckman, Heather L.; Meng, Xiaolei; Nassal, Drew; Moise, Nicolae; Miller, Alec; Min, Dennison; Soltisz, Andrew M.; Anne, Midhun N.K.; Alves Dias, Patrícia A.; Wagnon, Jacy L.; Weinberg, Seth H.; Hund, Thomas J.; Veeraraghavan, Rengasayee; Radwański, Przemysław B.
Source
JACC: Clinical Electrophysiology; May 2024, Vol. 10 Issue: 5 p829-842, 14p
Subject
Language
ISSN
2405500X
Abstract
Sudden unexpected death in epilepsy (SUDEP) is a fatal complication experienced by otherwise healthy epilepsy patients. Dravet syndrome (DS) is an inherited epileptic disorder resulting from loss of function of the voltage-gated sodium channel, NaV1.1, and is associated with particularly high SUDEP risk. Evidence is mounting that NaVs abundant in the brain also occur in the heart, suggesting that the very molecular mechanisms underlying epilepsy could also precipitate cardiac arrhythmias and sudden death. Despite marked reduction of NaV1.1 functional expression in DS, pathogenic late sodium current (INa,L) is paradoxically increased in DS hearts. However, the mechanisms by which DS directly impacts the heart to promote sudden death remain unclear.