# The role of cardiac mitochondrial energetics in cardiac arrhythmias and SUDEP

> **NIH NIH R21** · EAST TENNESSEE STATE UNIVERSITY · 2021 · $58,969

## Abstract

Project Summary
Dravet Syndrome (DS) is a catastrophic pediatric epilepsy that largely arises from loss-of-function
mutations in sodium channel genes. Overlapping neuronal and cardiac expression patterns of mutant
sodium channels are proposed to underlie the pathophysiology of a number of genetic diseases that
exhibit both epileptic and cardiac phenotypes. The risk of sudden death in epilepsy patients is twenty
four times greater than the general population. Despite advances in recent years to understand the
mechanisms of Sudden Unexpected Death in Epilepsy (SUDEP), it has remained elusive. Proposed
mechanisms of SUDEP have implicated seizure-induced apnea, pulmonary edema, dysregulation of
cerebral circulation, autonomic dysfunction, or cardiac arrhythmias. Besides being the powerhouse of
the cell, the mitochondria is responsible for long term ionic balance in the cell and compromised
mitochondrial function may precede cardiac arrhythmias and epileptic events. Our central hypothesis is
that compromised mitochondrial energetics and ionic homeostasis predisposes DS patients to cardiac
arrhythmias, seizures, and SUDEP-like events. The parent project seeks to uncover novel mechanisms
by which cardiac excitability is altered due to compromised mitochondrial energetics in Dravet
Syndrome (DS) models, a form of epilepsy with a high incidence of SUDEP. This supplement will focus on
mitochondria mechanisms of epileptogenesis in DS. The significance of this project is that it fills a major
void in understanding the mechanism of SUDEP in DS and results from the proposed experiments have
the potential to lead to new therapeutic treatments in DS. While this grant focuses on the role of DS
mutations, it is our hope that these results may be applicable to other genetic and non-genetic
epilepsies that will be the focus of future projects. The proposed studies will provide valuable insight to
the field and may lead to the discovery of several potential therapeutic targets for DS. The mitochondria
represent an ideal target to investigate, as there is growing interest in the mitochondrial mechanisms of
arrhythmogenesis and novel drugs may soon be available to test in epilepsy models.

## Key facts

- **NIH application ID:** 10405287
- **Project number:** 3R21NS116647-01A1S1
- **Recipient organization:** EAST TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Chad Frasier
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $58,969
- **Award type:** 3
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405287

## Citation

> US National Institutes of Health, RePORTER application 10405287, The role of cardiac mitochondrial energetics in cardiac arrhythmias and SUDEP (3R21NS116647-01A1S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10405287. Licensed CC0.

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