Affiliation:
1. Kazan State Medical University, Ministry of Health of the Russian Federation
Abstract
The purpose of the paper is to analyze possible mechanisms of ictal activity at the synaptic level in epilepsy.
Materials and Methods. The search for literature sources was carried out in Pubmed, CyberLeninka, and Google Scholar.
Results. The diversity of pathophysiological mechanisms of epilepsy makes it difficult to treat approximately one third of patients, whose ictal activity is not suppressed by traditional pharmacological agents.
The increased glutamate effect may be a consequence of its increased concentration in the intercellular space due to impaired reuptake caused by dysfunction of the EAATs transporters. Excitatory influences can also be enhanced by reduced connexin 43 (Cx43) expression in the synaptic cleft and downregulation of Kir4.1 inward rectifying potassium channel, which increases the extracellular concentration of K+ and glutamate causing neuron hyperexcitability.
Disturbances in neuronal, glial or neuronal-glial interactions have a similar effect. This is caused by malfunctioning of ionotropic or metabotropic receptors due to abnormal expression of astrocytic glutamate transporters and/or malfunction of neuronal or astrocytic enzymes.
One of the proteins involved in epileptogenesis is aquaporin (AQP4). Altered AQP4 expression potentially affects potassium reuptake by Kir 4.1 and glutamate reuptake and reduces glutamate transporter EAAT2 expression. AQP4 can also interact with glutamate receptor mGluR5.
Decreased GABAergic signaling may result from decreased numbers of GABAergic neurons in glial diseases and tumors. Besides, due to a decrease in plasmalemmal expression of the chloride cotransporter KCC2 and an increase in the expression of NKCC1 (Na-K-2Cl cotransporter), the intracellular concentration of CI– ions increases. As a result, GABA performs a depolarizing, excitatory role.
Conclusion. The pathophysiological mechanisms of epilepsy may become a target in the development of new drugs with anticonvulsant effects.
Publisher
Ulyanovsk State University
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