Ionotropic excitatory amino acid receptors in pre-Botzinger complex play a modulatory role in hypoxia-induced gasping in vivo.
Activation of ionotropic excitatory amino acid (EAA) receptors in pre-Bötzinger complex (pre-BötC) not only influences the eupneic pattern of phrenic motor output but also modifies hypoxia-induced gasping in vivo by increasing gasp frequency. Although ionotropic EAA receptor activation in this region appears to be required for the generation of eupneic breathing, it remains to be determined whether similar activation is necessary for the production and/or expression of hypoxia-induced gasping. Therefore, we examined the effects of severe brain hypoxia before and after blockade of ionotropic EAA receptors in the pre-BötC in eight chloralose-anesthetized, deafferented, mechanically ventilated cats. In each experiment, before blockade of ionotropic EAA receptors in the pre-BötC, severe brain hypoxia (6% O2 in a balance of N2 for 3-6 min) produced gasping. Although bilateral microinjection of the broad-spectrum ionotropic EAA receptor antagonist kynurenic acid (20-100 mM; 40 nl) into the pre-BötC eliminated basal phrenic nerve discharge, severe brain hypoxia still produced gasping. Under these conditions, however, the onset latency to gasping was increased (P < 0.05), the number of gasps was reduced for the same duration of hypoxic gas exposure (P < 0.05), the duration of gasps was prolonged (P < 0.05), and the duration between gasps was increased (P < 0.05). These findings demonstrate that hypoxia-induced gasping in vivo does not require activation of ionotropic EAA receptors in the pre-BötC, but ionotropic EAA receptor activation in this region may modify the expression of the hypoxia-induced response. The present findings also provide additional support for the pre-BötC as the primary locus of respiratory rhythm generation.
Solomon
Irene C
IC
Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, NY 11794-8661, USA. icsolomon@physiology.pnb.sunysb.edu
D000818:Animals; D002415:Cats; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008845:Microinjections; D010791:Phrenic Nerve / Q000187:drug effects / Q000503:physiopathology; D011930:Reaction Time; D017470:Receptors, Glutamate / Q000378:metabolism*; D012125:Respiratory Center / Q000187:drug effects / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D007736:Kynurenic Acid