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Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001
Received 14 March 1996; accepted in final form 11 June 1996.
Nattie, Eugene E., and Aihua Li. Central
chemoreception in the region of the ventral respiratory group in the
rat. J. Appl. Physiol. 81(5):
1987-1995, 1996.
We injected acetazolamide (AZ; 5 × 10
6 M, 1 nl) into the
region of the ventral respiratory group (VRG) of anesthetized paralyzed
ventilated rats. Control injections (mock cerebrospinal fluid,
n = 6, or the inactive AZ analogue 2-acetylamino-1,3,4-thiadiazole-5-sulfon-t-butylamide,
n = 6) did not increase the integrated
phrenic neurogram [phrenic nerve amplitude (PNA)]. The AZ
injections produced a focal region of tissue acidosis with a radius < 300-400 µm and are used as a probe for sites of central
chemosensitivity. Injection location is determined by anatomic
analysis. Of 22 VRG injections of AZ, 14 increased the amplitude of the
PNA over 15-90 min; 8 had no effect. In 17 cases, we measured
medullary tissue pH at the injection center and/or at a distant
site and reaffirmed the size of the acidotic region produced by such
small AZ injections. Of injections with pH electrodes within
300-400 µm of the injection center, all responders showed an
acid pH; three nonresponders showed an acid pH, and one an alkaline pH.
In a subgroup of five rats, at VRG sites with known respiratory effects
identified by prior glutamate injection (10 nl, 100 mM), all subsequent
AZ injections produced a PNA response. Simultaneous measurement of PNA
and tissue pH responses at the injection center of eight rats did not
show a uniform correlation in time; initially, both changed with a
similar time course, but PNA recovered more quickly. We conclude that
1) the region of the VRG contains
sites of ventilatory chemoreception,
2) ineffective AZ injections do
produce a tissue acidosis but at sites with minimal impact on
breathing, and 3) tissue
pH does not uniquely represent the chemoreceptor stimulus.
ventral medulla; control of breathing; carbon dioxide sensitivity; central chemoreceptors
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