Afferent Input from Peripheral Chemoreceptors in Response to Hypoxia and Amino Acid Neurotransmitter Generation in the Medulla

Abstract

The ventilatory response to acute hypoxia is biphasic with an initial hyperventilatory response followed by a fall in ventilation within a few minutes (roll-off) to levels above the pre-hypoxic values, but below the peak. The physiological sequence of events underlying the biphasic ventilatory response to hypoxia has not been completely elucidated. Different experimental approaches suggest that both local (i.e., neurochemical activity) and global (i.e., metabolic) mechanisms may very well be crucial during this transient phase of ventilatory hypoxic response. Numerous investigations (Bianchi et al, 1995; Weil, 1994), as well as work in our own laboratory (Kazemi et al, 1989; Hoop et al, 1990; Kazemi & Hoop, 1990), have directed attention to a possible central locus of the phenomenon in the ventrolateral medullary surface (VMS). The excitatory amino acid glutamate and the inhibitory amino acids γ-aminobutyric acid (GABA) and glycine appear to have special roles to play in the response. Namely, afferent stimuli from peripheral chemoreceptors lead to release of excitatory glutamate in the intermediate area of the VMS which cause the increase in central ventilatory output (Soto-Arape et al, 1995). Brain hypoxia also causes a rise in inhibitory GABA and glycine which then diminishes respiratory neuronal output.