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

• Published in: Epilepsy research 2019-12, Vol.158, p.106224-106224, Article 106224
• Main Authors: Gaidin, Sergei G., Zinchenko, Valery P., Teplov, Ilia Y., Tuleukhanov, Sultan T., Kosenkov, Artem M.
• Format: Article
• Language: English
• Subjects: AMPA receptors; Ca2+ conductivity; Epileptiform activity; Kainate receptors; NMDA receptors; Voltage-gated Ca2+-channels
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2019.106224

•The burst-firing pattern in Mg2+-free medium differs from spontaneous bursts.•The removal Mg2+ from the medium stimulates the release of glutamate.•Mg2+-free conditions cause decreased calcium conductivity of glutamate receptors. 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.