Excitatory amino acid receptors of guinea pig medial nucleus tractus solitarius neurons

Neurons isolated from the medial subnuclei of nucleus tractus solitarius in adult guinea pigs were studied for responses to the excitatory amino acid glutamate and its analogues using the whole cell tight-seal voltage clamp technique. In 80% of the cells studied (n = 60) 100 microM glutamate produced inward currents at negative voltages. To further characterize the glutamate response, the agonists for three glutamate receptor subtypes, N-methyl-D-aspartate (NMDA), kainate, and quisqualate, were examined for their effects on membrane conductance. NMDA (25-250 microM) activated currents in 85% of the neurons tested (n = 30). NMDA currents were generally very small in amplitude. Of the neurons tested, 84% responded to kainate (10-30 microM, n = 19) and only 50% to quisqualate (25-50 microM, n = 26). The conductance activated by NMDA was outwardly rectifying. The conductance activated by kainate was voltage independent, while that activated by quisqualate showed varying degrees of outward rectification. Responses to NMDA were specifically antagonized by DL-2-amino-5-phosphonovaleric acid (AP-5, 50-100 microM). Kainate responses were blocked by kynurenate at concentrations (0.5-1.5 mM) ineffective on quisqualate-induced current. Glutamic acid diethyl ester (GDEE, 2-15 mM) was effective in reducing quisqualate responses at concentrations that had no effect on kainate responses. This characterization of the glutamate receptor subtypes and effective antagonists provides a basis for future determination of the specific receptor of glutamate responsible for mediation of the excitatory postsynaptic potentials produced by activation of the baroreceptor input.