# Potential roles of voltage-gated ion channel disruption in Tuberous Sclerosis Complex

## TL;DR

This paper explores how disrupted voltage-gated ion channels may contribute to epilepsy in Tuberous Sclerosis Complex, a genetic disorder linked to mTOR signaling.

## Contribution

The paper introduces a novel perspective on Tuberous Sclerosis Complex by linking mTOR signaling to voltage-gated ion channel dysfunction in epilepsy.

## Key findings

- Tuberous Sclerosis Complex is associated with overactive mTOR signaling and a high incidence of epilepsy.
- Voltage-gated ion channel mutations can alter neuronal excitability and cause seizures.
- Emerging data suggests mTOR signaling may regulate voltage-gated ion channel expression in neurons.

## Abstract

Tuberous Sclerosis Complex (TSC) is a lynchpin disorder, as it results in overactive mammalian target of rapamycin (mTOR) signaling, which has been implicated in a multitude of disease states. TSC is an autosomal dominant disease where 90% of affected individuals develop epilepsy. Epilepsy results from aberrant neuronal excitability that leads to recurring seizures. Under neurotypical conditions, the coordinated activity of voltage-gated ion channels keep neurons operating in an optimal range, thus providing network stability. Interestingly, loss or gain of function mutations in voltage-gated potassium, sodium, or calcium channels leads to altered excitability and seizures. To date, little is known about voltage-gated ion channel expression and function in TSC. However, data is beginning to emerge on how mTOR signaling regulates voltage-gated ion channel expression in neurons. Herein, we provide a comprehensive review of the literature describing common seizure types in patients with TSC, and suggest possible parallels between acquired epilepsies with known voltage-gated ion channel dysfunction. Furthermore, we discuss possible links toward mTOR regulation of voltage-gated ion channels expression and channel kinetics and the underlying epileptic manifestations in patients with TSC.