CENTRAL CHEMORECEPTION IN THE REGION OF THE VENTRAL RESPIRATORY GROUPIN THE RAT

We injected acetazolamide (AZ; 5 x 10(-6) M, 1 nl) into the region of the ventral respiratory group (VRG) of anesthetized paralyzed ventilat ed rats. Control injections (mock cerebrospinal fluid, n = 6, or the i nactive AZ analogue etylamino-1,3,4-thiadiazole-5-sulfon-t-butylamide, n = 6) did not increase the integrated phrenic neurogram [phrenic ner ve amplitude (PNA)]. The AZ injections produced a focal region of tiss ue acidosis with a radius < 300-400 mu m and are used as a probe for s ites of central chemosensitivity. Injection location is determined by anatomic analysis. Of 22 VRG injections of AZ, 14 increased the amplit ude of the PNA over 15-90 min; 8 had no effect. In 17 cases, we measur ed medullary tissue pH at the injection center and/or at a distant sit e and reaffirmed the size of the acidotic region produced by such smal l AZ injections. Of injections with pH electrodes within 300-400 pm of the injection center, all responders showed an acid pH; three nonresp onders showed an acid pH, and one an alkaline pH. In a subgroup of fiv e rats, at VRG sites with known respiratory effects identified by prio r glutamate injection (10 nl, 100 mM), all subsequent AZ injections pr oduced a PNA response. Simultaneous measurement of PNA and tissue pH r esponses at the injection center of eight rats did not show a uniform correlation in time; initially, both changed with a similar time cours e, but PNA recovered more quickly. We conclude that 1) the region of t he VRG contains sites of ventilatory chemoreception, 2) ineffective AZ injections do produce a tissue acidosis but at sites with minimal imp act on breathing, and 3) tissue pH does not uniquely represent the che moreceptor stimulus.