Differential roles for NMDA and non-NMDA receptor subtypes in baroreceptor afferent integration in the nucleus of the solitary tract of the rat.
1. Microinjection studies have established that both NMDA and non-NMDA excitatory amino acid (EAA) receptor subtypes are involved in the integration of baroreceptor afferent inputs within the nucleus of the solitary tract (NTS). The present study was undertaken to determine which EAA receptor subtypes are involved in baroreceptor afferent integration by second and higher order NTS neurones. 2. Experiments utilizing intracellular recordings or extracellular recordings with microiontophoresis were performed in pentobarbitone-anaesthetized, paralysed and artificially ventilated rats to determine the ionotropic EAA receptor subtypes involved in baroreceptor afferent integration in the NTS. NTS neurones were classified according to their responses to aortic depressor nerve (ADN) stimulation: monosynaptic neurones (MSNs), polysynaptic neurones (PSNs) and ADN-non-evoked neurones (NENs). 3. In the extracellular studies, the ADN-evoked discharge of most MSNs was selectively reduced by microiontophoretic application of the non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; n = 8, P < 0.05) or 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo(f)quinoxaline-7-sulphonamide (NBQX; n = 9, P < 0.01), but not by the NMDA antagonist dl-2-amino-5-phosphonopentanoic acid (AP-5; n = 6, P = 0.28). ADN-evoked responses of PSNs were attenuated by microiontophoretic application of AP-5 (n = 12, P < 0. 001), CNQX (n = 13, P < 0.001) or NBQX (n = 11, P < 0.001). All EAA antagonists inhibited the spontaneous discharge of MSNs/PSNs and NENs (P < 0.01 for each group). 4. In the intracellular studies, ADN stimulation evoked faster rising and shorter duration excitatory postsynaptic potentials (EPSPs) in MSNs (n = 16) than in PSNs (n = 15) (P < 0.05 for each comparison). 5. Our results demonstrate that synaptic inputs from ADN to MSNs have faster rise times and shorter durations than those to PSNs, suggesting that baroreceptor inputs to MSNs and PSNs are mediated by different synaptic mechanisms. These more rapid synaptic events are selectively mediated by non-NMDA receptors. In addition, synaptic integration of ADN inputs by PSNs is mediated by both NMDA and non-NMDA receptors. Finally, the ADN-evoked discharge of some MSNs and PSNs is not attenuated by ionotropic EAA antagonists, suggesting that another receptor or transmitter system may mediate synaptic excitation in these neurones.
Department of Pharmacology, The University of Texas Health Science Center, San Antonio, TX 78284-7764, USA. ZhangJ@uthscsa.edu
J
J
Zhang
S W
SW
Mifflin
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007478:Iontophoresis; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009475:Neurons, Afferent / Q000737:chemistry* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000737:chemistry*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D017552:Solitary Nucleus / Q000737:chemistry / Q000166:cytology*; D013569:Synapses / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D016202:N-Methylaspartate; D010656:Phenylephrine; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014662:Vasoconstrictor Agents; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline