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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

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

¹Department of Biology, St. Lawrence University, Canton, New York 13617; and ²Department 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 CO₂ 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 CO₂ (FI_CO2 = 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% CO₂ (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 <11 wk of age, but V_E and V_T were increased 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 CO₂ 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 CO₂ in younger animals, but appear to inhibit the ventilatory response to CO₂ in older animals.

retrotrapezoid nucleus; acetazolamide; spironolactone

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