Epileptiform activity promotes decreasing of Ca2+ conductivity of NMDARs, AMPARs, KARs, and voltage-gated calcium channels in Mg2+-free model.

Abstract:

:NMDA, AMPA, and kainate receptors are the principal excitatory receptors in the brain. These receptors have been considered as the main targets in the treatment of epilepsy in recent years. This work aimed to determine how the Ca2+ conductivity of ionotropic glutamate receptors and voltage-gated Ca2+ channels changes in an in vitro model of epilepsy. For induction of epileptiform activity, hippocampal neurons were exposed to Mg2+-free medium. It has been shown that removal of Mg2+ from the medium not only removes the block from the NMDA receptors but also stimulates the release of glutamate in a way that is independent of the NMDA receptors. Under these conditions, the structure of the bursts significantly differs from the spontaneous bursts arising in mature hippocampal cultures. We have demonstrated that the frequency and amplitude of Mg2+-free medium-induced Ca2+ oscillations decrease after the 60-min exposure. Besides, the Ca2+ conductivity of ionotropic glutamate receptors and voltage-gated calcium channels significantly reduces. Thus, the decrease of Ca2+ conductivity can be considered as one of the mechanisms of adaptation during epilepsy.

journal_name

Epilepsy Res

journal_title

Epilepsy research

authors

Gaidin SG,Zinchenko VP,Teplov IY,Tuleukhanov ST,Kosenkov AM

doi

10.1016/j.eplepsyres.2019.106224

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

106224

eissn

0920-1211

issn

1872-6844

pii

S0920-1211(19)30402-4

journal_volume

158

pub_type

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