| Abstract: | Glia are thoughtto be important in brain extracellular fluid ion and pH regulation, buttheir role in brain stem sites that sense pH and stimulate breathing isunknown. Using a diffusion pipette, we administered the glial toxin,fluorocitrate (FC; 1 mM) into one such brain stem region, theretrotrapezoid nucleus (RTN) for 45-60 min. This dose and timeperiod were chosen so that the effects of FC would be largelyreversible. Within minutes, tissue pH decreased, and respiratory outputincreased. Both recovered almost completely after cessation of FCadministration. The response to systemicCO2 stimulation was unaffected byFC treatment compared with that following control diffusion. Anatomicanalysis showed, at the center of FC administration, some small (meandiameter = 5.1 µm) cells that stained for DEAD Red, a marker foraltered cell membrane permeability, and some fragmented glia (glialfibrillary acidic protein immunohistochemistry). The average RTN tissuevolume that contained such DEAD Red-positive cells was 271 nl, ~23%of the volume of one RTN region. Reversible disruption of glia in theRTN, a region known to contain central chemoreception, results in anacidic local pH and in stimulation of respiratory output. |
