Ventilatory effects of gap junction blockade in the RTN in awake rats.
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) (Fi(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 microM) or hypercapnic artificial cerebrospinal fluid equilibrated with 50% CO(2) (pH approximately 6.5). Focal perfusion of AZ or hypercapnic aCSF increased V(E), V(T), and F(R) during exposure to room air. Carbenoxolone (300 microM) 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 microM) 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.
Department of Biology, St. Lawrence University, Canton, NY 13617, USA.
Amy
A
Hewitt
Rachel
R
Barrie
Michael
M
Graham
Kara
K
Bogus
J C
JC
Leiter
Joseph S
JS
Erlichman
D000086:Acetazolamide / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D015656:Respiratory Mechanics; D014851:Wakefulness / Q000502:physiology*
D002229:Carbenoxolone; D000086:Acetazolamide