Publication
Title
Loss of synaptic transporter function increases risk of febrile seizures
Author
Abstract
Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn2+) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn2+ homeostasis contributes to susceptibility is unknown. Synaptic Zn2+ is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn2+ into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C > T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn2+ increases the risk of FS and more broadly support the idea that impaired synaptic Zn2+ homeostasis can contribute to neuronal hyperexcitability.
Language
English
Source (journal)
Scientific reports. - London, 2011, currens
Publication
London : Nature Publishing Group, 2015
ISSN
2045-2322
Volume/pages
5(2015), 9 p.
Article Reference
17816
ISI
000366035800001
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 15.01.2016
Last edited 20.06.2017
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