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The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type Ca2+ currents by altering calnexin-dependent trafficking of Ca(v)3.2 channels

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00479170" target="_blank" >RIV/61388963:_____/17:00479170 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.nature.com/articles/s41598-017-11591-5" target="_blank" >https://www.nature.com/articles/s41598-017-11591-5</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1038/s41598-017-11591-5" target="_blank" >10.1038/s41598-017-11591-5</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type Ca2+ currents by altering calnexin-dependent trafficking of Ca(v)3.2 channels

  • Original language description

    Low-voltage-activated T-type calcium channels are essential contributors to the functioning of thalamocortical neurons by supporting burst-firing mode of action potentials. Enhanced T-type calcium conductance has been reported in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and proposed to be causally related to the overall development of absence seizure activity. Here, we show that calnexin, an endoplasmic reticulum integral membrane protein, interacts with the III-IV linker region of the Ca(v)3.2 channel to modulate the sorting of the channel to the cell surface. We demonstrate that the GAERS missense mutation located in the Ca(v)3.2 III-IV linker alters the Ca(v)3.2/calnexin interaction, resulting in an increased surface expression of the channel and a concomitant elevation in calcium influx. Our study reveals a novel mechanism that controls the expression of T-type channels, and provides a molecular explanation for the enhancement of T-type calcium conductance in GAERS.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30105 - Physiology (including cytology)

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2017

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Scientific Reports

  • ISSN

    2045-2322

  • e-ISSN

  • Volume of the periodical

    7

  • Issue of the periodical within the volume

    Sep 14

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    13

  • Pages from-to

  • UT code for WoS article

    000410739000011

  • EID of the result in the Scopus database

    2-s2.0-85029477490