Widespread sites of brain stem ventilatory chemoreceptors

Abstract

We produced local tissue acidosis in various brain stem regions with 1-nl injections of acetazolamide (AZ) to locate the sites of central chemoreception. To determine whether the local acidosis resulted in a stimulation of breathing, we performed the experiment in chloralose-urethan anesthetized vagotomized carotid-denervated (cats) paralyzed servo-ventilated cats and rats and measured phrenic nerve activity (PNA) as the response index. Measurements of extracellular brain tissue pH by glass microelectrodes showed that AZ injections induced a change in pH at the injection center equivalent to that produced by an increase in end-tidal PCO2 of approximately 36 Torr and that the change in brain pH was limited to a tissue volume with a radius of < 350 microns. We found AZ injections sites that caused a significant increase in PNA to be located 1) within 800 microns of the ventrolateral medullary surface at locations within traditional rostral and caudal chemosensitive areas and the intermediate area, 2) within the vicinity of the nucleus tractus solitarii, and 3) within the vicinity of the locus coeruleus. Single AZ injections produced increases in PNA that were < or = 69% of the maximum value observed with an increase in end-tidal PCO2. We conclude that central chemoreceptors are distributed at many locations within the brain stem, all within 1.5 mm of the surface, and that stimulation of a small fraction of all central chemoreceptors can result in a large ventilatory response.

Characterization of the chemosensitive response of individual solitary complex neurons from adult rats

“…The normal response of pH i to an NH 4 Cl prepulse is a rapid alkalinization followed by an acidification in the absence of any change in extracellular pH (2,42). We found that the response to NH 4 Cl of SC neurons from adult rats was similar to that of SC neurons from neonatal rats (41,42). Adult SC neurons exhibited a rapid pH i recovery from an NH 4 Cl prepulse induced acidification that returned toward the initial pH i (Fig.…”

“…The steady-state pH i in SC neurons from adult rats is 7.30 Ϯ 0.03 (n ϭ 27), significantly (P Ͻ 0.001) less alkaline than the value of 7.49 Ϯ 0.02 previously reported for SC neurons from neonatal rats (42). The NH 4 Cl prepulse technique was used to study the pH i responses of SC neurons from adult rats. The normal response of pH i to an NH 4 Cl prepulse is a rapid alkalinization followed by an acidification in the absence of any change in extracellular pH (2,42).…”

“…The NH 4 Cl prepulse technique was used to study the pH i responses of SC neurons from adult rats. The normal response of pH i to an NH 4 Cl prepulse is a rapid alkalinization followed by an acidification in the absence of any change in extracellular pH (2,42). We found that the response to NH 4 Cl of SC neurons from adult rats was similar to that of SC neurons from neonatal rats (41,42).…”

“…All of these regions increase ventilation when focally acidified (4,26). Specifically, in the NTS, it was found that when the rostral region was focally acidified, there was a small increase in ventilation, but when the caudal region of the NTS was focally acidified, there was a large increase in ventilation (27).…”

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

“…First, chronic hypoxia changes the ventilatory response to CO 2 (60), and the NTS contains CO 2 -sensitive cells (11,14,43). Also, the NTS receives the first synapse from O 2 -sensitive afferents from the carotid bodies (15,21,22,33,59), and this could lead to hypoxic or activity-dependent plasticity that has been demonstrated in the central nervous system with chronic hypoxia (16,49,62).…”