Ventilatory effects of gap junction blockade in the RTN in awake rats

1 Department of Biology, St. Lawrence University, Canton, New York 13617; and 2 Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756 Submitted 22 June 2004 ; accepted in final form 30 July 2004 We tested the hypothesis that carbenoxolone, a pharmacological inhibitor of gap junctions, would reduce the ventilatory response to CO 2 when focally perfused within the retrotrapezoid nucleus (RTN). We tested this hypothesis by measuring minute ventilation (V E ), tidal volume (V T ), and respiratory frequency (F R ) responses to increasing concentrations of inspired CO 2 (F I CO 2 = 0–8%) in rats during wakefulness. We confirmed that the RTN was chemosensitive by perfusing the RTN unilaterally with either acetazolamide (AZ; 10 µM) or hypercapnic artificial cerebrospinal fluid equilibrated with 50% CO 2 (pH 6.5). Focal perfusion of AZ or hypercapnic aCSF increased V E , V T , and F R during exposure to room air. Carbenoxolone (300 µM) focally perfused into the RTN decreased V E and V T in animals 12 wk of age. Glyzyrrhizic acid, a congener of carbenoxolone, did not change V E , V T , or F R when focally perfused into the RTN. Carbenoxolone binds to the mineralocorticoid receptor, but spironolactone (10 µM) did not block the disinhibition of V E or V T in older animals when combined with carbenoxolone. Thus the RTN is a CO 2 chemosensory site in all ages tested, but the function of gap junctions in the chemosensory process varies substantially among animals of different ages: gap junctions amplify the ventilatory response to CO 2 in younger animals, but appear to inhibit the ventilatory response to CO 2 in older animals. retrotrapezoid nucleus; acetazolamide; spironolactone Address for reprint requests and other correspondence: J. S. Erlichman, Dept. of Biology, St. Lawrence Univ., Canton, NY 13617 (E-mail: jerlichman{at}stlawu.edu )