Blocking of glutamate ionotropic receptors: Influence on the respiratory activity generated by medullo-spinal preparations of rats in hypoxia

Abstract

We studied the influences of a non-competitive blocker of glutamate NMDA-receptors ketamune and of a competitive blocker of AMPA-kainate non-NMDA receptors, CNQX, on the respiratory activity generelated by superfusedin situ semi-isolated medullo-spinal preparations (SIMSP) of 3- to 4-day-old rats. We compared the ampes recorded under conditions of superfusion, a standard solution and the solution saturated with an anoxic isocapine gas mixture were compared; pO2 in these solutions were 440±22 and 41±8 mm Hg, respectively. The experments were carried out with the ventrolateral medullary region (VLMR) left intact or after separation of its rostral part, which propertchonally corresponded to the chemosensitiveM zone. A 3-min-long hypoxic test initially evoked an increase in the frequency of inspiratory discharges (IR) in the phrenic nerve followed by a frequency drop within the final half of the test. After the rostral VLMR had been separated, the hypoxic test did not elicit a significant decrease in the IR frequency. After preliminary application of 1.0 or 10.0 μM ketamine or CNQX on intact preparations, the IR frequency under hypoxic conditions dropped within the first half of the test and increased in the second half, while the amplitude and integral intensity of these discharges were depressed more intensively than in hypoxia with no applications. Using ketamme and CNQX in the same concentrations resulted in significant drops in the amplitude, frequency, and integral intensity of IR recorde din the hypoxic test. Our experiments showed that in the early postnatal period glutamate ionotropic receptors of rostral VLMR neurons are involved in the control of IR frequency under hypoxic conditions. The possible role of glutamatergic control of the respiratory rhythm and mechanisms of the influences resulting from blocking of NMDA and non-NMDA receptors on the parameters of respiratory activity are discussed.