Влияние антагонистов NMDA рецепторов разных типов на вызванные ответы пирамидных нейронов в срезах коры мозга крысы

Abstract

The use of NMDA receptor antagonists for the treatment of CNS diseases is currently limited. This may be due to the lack of knowledge about the effects of antagonists on the functional properties of neurons since in vitro models do not fully reproduce the real pathophysiological processes. We studied the effects of NMDA receptor antagonists on properties of pyramidal neuron responses in the rat prefrontal cortex. A competitive antagonist APV (50 µM) and an ion channel blocker memantine (100 µM) did not produce significant effects on evoked EPSP. When the inhibitory transmission was suppressed by picrotoxin (50 µM), the extracellular stimulation caused prolonged membrane depolarization and generation a series of action potentials. APV decreased duration and amplitude of such responses. Memantine was active only when magnesium was excluded from the extracellular environment. The lack of effects of memantine can be explained by its competition with magnesium for the binding site within the ion channel. This work demonstrates that in order to predict the systemic effects of blockers on the functions of neurons and their excitability, it is necessary to use in vitro models in which the activation of NMDA receptors occurs in the presence of physiological concentrations of magnesium and without clamping of membrane potential.