Voltage‐gated sodium channels in genetic epilepsy: up and down of excitability
Abstract
The past two decades have witnessed a wide range of studies investigating genetic variants of voltage‐gated sodium (NaV) channels, which are involved in a broad spectrum of diseases, including several types of epilepsy. We have reviewed here phenotypes and pathological mechanisms of genetic epilepsies caused by variants in Na V α and β subunits, as well as of some relevant interacting proteins ( FGF12/FHF1 , PRRT2, and Ankyrin‐G). Notably, variants of all these genes can induce either gain‐ or loss‐of‐function of Na V leading to either neuronal hyperexcitability or hypoexcitability. We present the results of functional studies obtained with different experimental models, highlighting that they should be interpreted considering the features of the experimental system used. These systems are models, but they have allowed us to better understand pathophysiological issues, ameliorate diagnostics, orientate genetic counseling, and select/develop therapies within a precision medicine framework. These studies have also allowed us to gain insights into the physiological roles of different NaV channels and of the cells that express them. Overall, our review shows the progress that has been made, but also the need for further studies on aspects that have not yet been clarified. Finally, we conclude by highlighting some significant themes of general interest that can be gleaned from the results of the work of the last two decades.T
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BibTeX
@article{rusina2026voltagegated,
title = {{Voltage‐gated sodium channels in genetic epilepsy: up and down of excitability}},
author = {Evgeniia Rusina and Martina Simonti and Fabrice Duprat and Sandrine Cestèle and Massimo Mantegazza},
journal = {Journal of Neurochemistry},
year = {2026},
month = oct,
doi = {10.1111/jnc.15947},
url = {https://hal.science/hal-04768542v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Voltage‐gated sodium channels in genetic epilepsy: up and down of excitability
AU - Evgeniia Rusina
AU - Martina Simonti
AU - Fabrice Duprat
AU - Sandrine Cestèle
AU - Massimo Mantegazza
PY - 2026
DA - 2026/10/09
JO - Journal of Neurochemistry
DO - 10.1111/jnc.15947
UR - https://hal.science/hal-04768542v1
AB - The past two decades have witnessed a wide range of studies investigating genetic variants of voltage‐gated sodium (NaV) channels, which are involved in a broad spectrum of diseases, including several types of epilepsy. We have reviewed here phenotypes and pathological mechanisms of genetic epilepsies caused by variants in Na V α and β subunits, as well as of some relevant interacting proteins ( FGF12/FHF1 , PRRT2, and Ankyrin‐G). Notably, variants of all these genes can induce either gain‐ or loss‐of‐function of Na V leading to either neuronal hyperexcitability or hypoexcitability. We present the results of functional studies obtained with different experimental models, highlighting that they should be interpreted considering the features of the experimental system used. These systems are models, but they have allowed us to better understand pathophysiological issues, ameliorate diagnostics, orientate genetic counseling, and select/develop therapies within a precision medicine framework. These studies have also allowed us to gain insights into the physiological roles of different NaV channels and of the cells that express them. Overall, our review shows the progress that has been made, but also the need for further studies on aspects that have not yet been clarified. Finally, we conclude by highlighting some significant themes of general interest that can be gleaned from the results of the work of the last two decades.T
SN - 0022-3042
SN - 1471-4159
ER -