Role of glutamate in the nucleus isthmi on the hypoxia- and hypercarbia-induced hyperventilation of toads.

The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain that has been reported to participate in CO(2) chemoreception and in the ventilatory response to hypoxia. In the present study, we assessed the role of glutamatergic transmission inside the NI on the hypoxic and hypercarbic drive to breathing. We compared the respiratory responses to 7 and 5% inspired O(2) and 3% inspired CO(2) after microinjecting 10 nmol/100 nl of kynurenic acid (an antagonist of L-glutamate receptors) into the NI of toads (Bufo paracnemis). Kynurenic acid had no effect under resting conditions. Both hypoxia and hypercarbia elicited an increase in ventilation in all groups, with hypoxia acting on tidal volume (V(T)) and hypercarbia on frequency (f). The microinjection of kynurenic acid into the NI caused an increased ventilatory response to hypoxia and hypercarbia due to a higher V(T). We conclude that glutamatergic transmission in the NI has an inhibitory effect when the respiratory drive is high, acting on V(T).