Involvement of NMDA Receptor in the Modulation of Excitatory and Inhibitory Amino Acid Neurotransmitters Release in Cortical Neurons

The purpose of this paper was to examine the function of N-methyl-D-aspartate (NMDA) glutamate receptor in cortical neurons on amino acid neurotransmitters release as well as the fraction of neurons implicated in the response of this receptor. Local stimulation of these cells at different concentrations of NMDA, agonist of this ionotropic glutamate receptor, produced a dose dependent release of aspartate, glutamate, glycine and GABA. These effects were blocked by DAP5, an antagonist of the NMDA receptor. The amino acid Ca²⁺ dependent release mediated by the NMDA receptor, is induced by the opening of voltage-dependent Ca²⁺ channels that this receptor promotes. Ca⁺⁺ movements were explored in single cells loaded with fura-2. When single cells were stimulated with 100 μM NMDA, the calcium recording performed showed that 82% of the cells responded to this agonist increasing the intracellular calcium concentration, although the amplitude of these increments was variable. The results suggest that NMDA-elicited neurotransmitter release from cortical neurons involves Ca²⁺-dependent and Ca²⁺-independent components, as well as neuron depolarisation, and different VDCC subtypes of N, P/Q or L depending of the amino acid neurotransmitter release elicited by this receptor.