Light-Driven Sodium Pump as a Potential Tool for the Control of Seizures in Epilepsy.

Autor: Trofimova AM; Sechenov Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg, Russia., Amakhin DV; Sechenov Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg, Russia., Postnikova TY; Sechenov Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg, Russia., Tiselko VS; Sechenov Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg, Russia., Alekseev A; Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology (National Research University), Dolgoprudny, Russia.; Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany., Podoliak E; Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology (National Research University), Dolgoprudny, Russia.; Department of Ophthalmology, Universitäts-Augenklinik Bonn, University of Bonn, Bonn, Germany., Gordeliy VI; Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology (National Research University), Dolgoprudny, Russia.; Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, Grenoble, France., Chizhov AV; Sechenov Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg, Russia.; MathNeuro Team, Inria Centre at Université Côte d'Azur, Sophia Antipolis, France., Zaitsev AV; Sechenov Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg, Russia. aleksey_zaitsev@mail.ru.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Jul; Vol. 61 (7), pp. 4691-4704. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1007/s12035-023-03865-z
Abstrakt: The marine flavobacterium Krokinobactereikastus light-driven sodium pump (KR2) generates an outward sodium ion current under 530 nm light stimulation, representing a promising optogenetic tool for seizure control. However, the specifics of KR2 application to suppress epileptic activity have not yet been addressed. In the present study, we investigated the possibility of KR2 photostimulation to suppress epileptiform activity in mouse brain slices using the 4-aminopyrindine (4-AP) model. We injected the adeno-associated viral vector (AAV-PHP.eB-hSyn-KR2-YFP) containing the KR2 sodium pump gene enhanced with appropriate trafficking tags. KR2 expression was observed in the lateral entorhinal cortex and CA1 hippocampus. Using whole-cell patch clamp in mouse brain slices, we show that KR2, when stimulated with LED light, induces a substantial hyperpolarization of entorhinal neurons. However, continuous photostimulation of KR2 does not interrupt ictal discharges in mouse entorhinal cortex slices induced by a solution containing 4-AP. KR2-induced hyperpolarization strongly activates neuronal HCN channels. Consequently, turning off photostimulation resulted in HCN channel-mediated rebound depolarization accompanied by a transient increase in spontaneous network activity. Using low-frequency pulsed photostimulation, we induced the generation of short HCN channel-mediated discharges that occurred in response to the light stimulus being turned off; these discharges reliably interrupt ictal activity. Thus, low-frequency pulsed photostimulation of KR2 can be considered as a potential tool for controlling epileptic seizures.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: