Does an Epilepsy Mutation Make Sodium Brain Channels More Excitable?
Faculty Mentor Information
Dr. James Groome, Idaho State University
Presentation Date
7-16-2026
Abstract
Voltage gated sodium channels are essential for action potentials in neurons. Sodium channel Nav1.2, in particular, has been strongly associated with a variety of neurological disorders. One variant of this channel, D1598N, has been linked to epilepsy. Despite its clinical relevance, the mechanisms by which D1598N alters channel function and contributes to disease is not fully characterized. To investigate this, wild-type hNaV1.2, the D1598N variant and the inactivation-deficient IQM mutant were expressed in Xenopus laevis oocytes by messenger RNA. Channel activity was then analyzed by utilizing cut open oocyte voltage clamp electrophysiology. Activation kinetics, activation probability, inactivation probability and recovery from inactivation were assessed under various protocols and compared among the variants. The results showed that the D1598N variant increased the probability of channel activation as a gain of function effect when compared to the wild type, which predicts neuronal hyperexcitability. Understanding how epilepsy associated variants can alter sodium brain channel function can contribute to a clearer understanding of the mechanism behind neurological disorder and can contribute to the development of targeted therapies for epilepsy.
Does an Epilepsy Mutation Make Sodium Brain Channels More Excitable?
Voltage gated sodium channels are essential for action potentials in neurons. Sodium channel Nav1.2, in particular, has been strongly associated with a variety of neurological disorders. One variant of this channel, D1598N, has been linked to epilepsy. Despite its clinical relevance, the mechanisms by which D1598N alters channel function and contributes to disease is not fully characterized. To investigate this, wild-type hNaV1.2, the D1598N variant and the inactivation-deficient IQM mutant were expressed in Xenopus laevis oocytes by messenger RNA. Channel activity was then analyzed by utilizing cut open oocyte voltage clamp electrophysiology. Activation kinetics, activation probability, inactivation probability and recovery from inactivation were assessed under various protocols and compared among the variants. The results showed that the D1598N variant increased the probability of channel activation as a gain of function effect when compared to the wild type, which predicts neuronal hyperexcitability. Understanding how epilepsy associated variants can alter sodium brain channel function can contribute to a clearer understanding of the mechanism behind neurological disorder and can contribute to the development of targeted therapies for epilepsy.