TY  - EJOU
AU  - Rubio, Carmen 
AU  - Serrano-García, Norma 
AU  - Lee, Ángel 
AU  - Pérez-Villavicencio, Javier 
AU  - Villa-Robledo, Omar 
AU  - Pimentel, Rodrigo Mercado 
AU  - Romo-Parra, Héctor 
AU  - Rubio-Osornio, Moisés 

TI  - The Intersection of Impaired Ion Channels and Depleted Mitochondria in Epileptic Seizures: A Narrative Review
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - Epilepsy is sustained by a self-reinforcing triad of ion channel dysfunction, mitochondrial impairment, and oxidative stress that lowers seizure threshold and drives epileptogenesis. This review examines how genetic channelopathies and redox-dependent post-translational modifications of voltage-gated sodium, calcium, and potassium channels disrupt excitatory–inhibitory balance, and how electron transport chain dysfunction amplifies reactive oxygen species, compromises adenosine triphosphate (ATP)-dependent membrane stability, and activates mechanistic target of rapamycin complex 1. Key convergences include oxidative ion channel modification, ATP-sensitive potassium channel impairment, synaptic lipid peroxidation, and gamma-aminobutyric acid (GABA)-ergic transporter dysfunction. Temporal lobe epilepsy is characterized by focal mitochondrial pathology, whereas genetic generalized epilepsies reflect thalamocortical channelopathies, a distinction with direct therapeutic implications. Precision strategies integrating mitochondria-targeted antioxidants, ion channel modulators, antioxidant supplementation N-acetylcysteine, α-lipoic acid, and mTOR inhibitors (rapamycin, everolimus) provide a mechanistic framework for interrupting the redox–metabolic–electrical feedback loop sustaining seizures and advancing disease modification.
KW  - Epilepsy; epileptogenesis; ion channelopathies; mitochondrial dysfunction; oxidative stress; mechanistic target of rapamycin complex 1; lipid peroxidation; redox signaling

DO  - 10.32604/biocell.2026.081478