Endogenous activation of NMDA and non-NMDA glutamate receptors on respiratory neurones in cat medulla.
The aim of this study was to evaluate the involvement of dicarboxylic amino acid neurotransmission in the periodic discharges of respiratory neurones. Respiratory neurones of the ventral and dorsal respiratory groups in the medulla of the cat were subjected to iontophoretic applications of (1) N-methyl-D-aspartate (NMDA) and a blocker of the NMDA subtype of glutamate receptor, D-2-amino-7-phosphonoheptanoic acid (AP7) and (2) an agonist and an antagonist of the non-NMDA subtypes of receptor: quisqualate and 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. All five main types of respiratory neurones (all-, early- and late-inspiratory, transitional "off-switch", late expiratory) were excited by NMDA and quisqualate. Both agonists increased the peak firing rate but exerted different effects on the discharge pattern of respiratory neurones, within the respiratory cycle. Quisqualate induced discharges in the "silent" period of the neurone more readily than did NMDA which, in turn had a more pronounced effect during the burst period of the neurone. The effects of quisqualate and NMDA were suppressed by prior application of their selective antagonists, AP7 and DNQX. These antagonists decreased the spontaneous neuronal discharge of all cell types, throughout the entire firing phase, by a maximum of 24-63% with AP7 and by 30-50% with DNQX. The non-selective antagonist, gamma-D-glutamyl-glycine and the selective NMDA antagonists, CPP and MK-801, were also effective. It is concluded that respiratory neurones, of all types, within the medullary respiratory network are subjected to endogenous glutamate-like excitations, which may possibly shape the respiratory train of action potentials through the sequential activation of non-NMDA and NMDA subtypes of receptor.
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Laboratoire de Physiologie Nerveuse, C.N.R.S., Gif-sur-Yvette, France.
Schmid
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Foutz
A S
AS
Denavit-Saubie
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002415:Cats; D003655:Decerebrate State; D007478:Iontophoresis; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D012125:Respiratory Center / Q000187:drug effects* / Q000502:physiology
D000596:Amino Acids; D011810:Quinoxalines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C056723:FG 9041; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; C031231:2-amino-7-phosphonoheptanoic acid