AMPA receptor activation of area postrema neurons

This study reports on the effects of activation of ionotropic glutamate receptors on area postrema neuron cytosolic calcium concentration ([Ca²⁺](i)]. In 140 of 242 area postrema neurons isolated from postnatal rats, application of 100 μM L-glutamate (L-Glu) resulted in a significant increase in [Ca²⁺](i). The remaining neurons were unaffected. The effects of L-Glu on area postrema [Ca²⁺](i) were dose dependent, with a threshold of response near 1.0 μM and maximal response near 100 μM. To determine if the response of L-Glu in area postrema neurons was due to activation of ionotropic glutamate receptors, the effects of the broad-spectrum ionotropic glutamate receptor antagonist kynurinic acid (Kyn) was determined. Application of 1.0 mM Kyn resulted in a 62.6 ± 4% inhibition of the L-Glu- evoked response. Application of the selective N-methyl-D-aspartic acid (NMDA) antagonist 2-amino-5-phosphonopentanoic acid had no effect on the response of area postrema neurons to 100 μM L-Glu. In contrast, application of the selective DL-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline (DNQX) effectively blocked the 100 μM L-Glu response. Application of (±)-AMPA mimicked the effects observed with L-Glu and was selectively blocked by DNQX. These results suggest that L-Glu activation of area postrema neurons involves activation of AMPA receptors but not NMDA receptors.