Key result
Mice with SCN8A mutation exhibited hyperexcitable heart cells, reduced heart rates mediated by parasympathetic changes, and ventricular arrhythmias when challenged with norepinephrine and caffeine.
Why the study?
Does SCN8A mutation cause cardiac arrhythmias and parasympathetic abnormalities in a mouse model of epileptic encephalopathy?
Does SCN8A mutation cause cardiac arrhythmias and parasympathetic abnormalities in a mouse model of epileptic encephalopathy?
SCN8A mutations in a mouse model lead to cardiac hyperexcitability, parasympathetic dysregulation, and ventricular arrhythmias, providing a potential mechanism for sudden unexpected death in epilepsy (SUDEP).
May prompt cardiac assessment in SCN8A epilepsy; leaves open impact on SUDEP prevention.
Significance Patients with epileptic encephalopathy have a high risk of sudden unexpected death in epilepsy (SUDEP), an event described as arrhythmia of brain and heart. We investigated the cardiac phenotype of a model of an epileptic encephalopathy caused by mutation of sodium channel SCN8A . We observed that mutant heart cells were hyperexcitable, exhibiting abnormal contraction and action potential wave forms. Mutant mice also had reduced heart rates compared with controls. This difference in heart rate was not observed in isolated hearts, implicating changes in cardiac regulation by the parasympathetic nervous system. When challenged with norepinephrine and caffeine, mutant mice had ventricular arrhythmias. These cardiac and parasympathetic abnormalities are predicted to contribute to the mechanism of SUDEP in patients with SCN8A mutations.
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Frasier et al. (2016) studied SCN8A epileptic encephalopathy. SCN8A mutation vs. Controls was evaluated on Cardiac phenotype (hyperexcitability, abnormal contraction, action potential wave forms, heart rate, ventricular arrhythmias). Mice with SCN8A mutation exhibited hyperexcitable heart cells, reduced heart rates mediated by parasympathetic changes, and ventricular arrhythmias when challenged with norepinephrine and caffeine.
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