Phrenic Nerve Response to Glutamate Antagonist Microinjection in the Ventral Medulla

Abstract

Effects of amino acid neurotransmitters on central respiratory drive roughly parallel their excitation or inhibition of neurons¹. The major amino acid neurotransmitter glutamic acid is of particular interest because it stimulates ventilatory drive centrally at sites and via mechanisms within the surface of the ventral medulla (VM). Glutamate metabolism in the brain is directly related to CO₂ metabolism and fixation in the brain. Decarboxylation of glutamate via the enzyme glutamic acid decarboxylase (GAD) localized substantially in nerve endings, results in formation of the inhibitory amino acid and central respiratory depressant, γ-aminobutyric acid (GABA)⁴. Recent studies^5,6 have shown that the classic biphasic ventilatory response to acute hypoxia has a glutamatergic component, namely, the initial hyperventilatory response is mediated in part by central glutamate. Topical application of glutamatergic receptor antagonists during normoxia to the surface of the VM diminishes central ventilatory drive via reduction in phrenic nerve output¹¹. The present study was therefore undertaken with multiple microinjections of the selective noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to localize in the VM the effects of blocking glutamate receptor on phrenic nerve output and to quantitate the effects via a model of chemoreceptor-antagonist interaction.