Effects of NMDA and non-NMDA receptor antagonists on the medullary inspiratory neuronal activity during spontaneous augmented breaths in anesthetized rats

Abstract

To elucidate whether there is a difference between the effects of iontophoretically applied N-methyl- d-aspartate (NMDA) and non-NMDA receptor antagonists on the activity of inspiratory neurons during spontaneous augmented breaths, extracellular single unit recording of inspiratory neurons (I-augmenting, I-decrementing and I-other) was performed in pentobarbital anesthetized rats. The spontaneous augmented breath was divided into two different phases; the first phase (phase I) resembled a normal inspiration, but the second phase (phase II) consisted of a marked increase in diaphragm electromyogram activity. The mean firing frequency of I-aug type neurons was significantly decreased after 50 nA application of both d-2-amino-5-phosphonopentanoic acid (AP-5) (NMDA receptor antagonist) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (non-NMDA receptor antagonist). The mean firing frequency of both I-dec and I-other neurons was significantly decreased by both AP-5 and CNQX applications (70 nA). After AP-5 application, relative changes in the discharge rates during inspiratory phases I and II of spontaneous augmented breaths were significantly suppressed in all types of neurons, but CNQX application had no significant effect on the response changes during phase II. In all cell types of neurons, a significant difference between the iontophoretic AP-5 and CNQX applications in the relative mean firing rate was observed. These results suggested that activation of the NMDA receptor-induced neurotransmission can modify the discharge rate of medullary inspiratory neurons, irrespective of the cell types, during the inspiratory phase II of spontaneous augmented breaths, but that non-NMDA receptor blockade may not significantly influence their discharge rate.