TESTING THE METABOLIC HYPOTHESIS OF O-2 CHEMORECEPTION IN THE CAT CAROTID-BODY IN-VITRO

It is known that oligomycin reduces the oxidative phosphorylation high-energy state or high-energy intermediates by inhibiting the formation of ATP without directly inhibiting electron transport, whereas metabolic uncouplers dissipate the high-energy state without net production of ATP. The metabolic hypothesis for O-2 chemoreception in the carotid body (CB) predicts that 1) oligomycin should diminish O-2 consumption and attenuate O-2 chemoreception and 2) uncouplers should reverse the effect of oligomycin by increasing O-2 consumption without restoring O-2 chemoreception. These predictions were tested by simultaneously measuring CB chemosensory discharge from the sinus nerve and the rate of tissue O-2 disappearance (dPo(2)/dt) during interruption of perfusate flow in perfused-superfused cat CB preparations (n = 9). O-2 consumption was calculated from dPo(2)/dt. Flow-interruption responses were measured before and after oligomycin (1-mu g bolus) and subsequently after dinitrophenol (50 mu M). Chemosensory responses to bolus injections of hypercapnic Tyrode solution, cyanide, or nicotine were also tested periodically. Oligomycin diminished dPo(2)/dt from -2.67 +/- 0.30 to -2.02 +/- 0.19 (SE) Torr/s (P < 0.004, paired t test) and reduced the maximal sensory response from 196 +/- 43 to 124 +/- 12 impulses/s (P < 0.002, paired t test) while augmenting the initial response to CO2. Dinitrophenol reversed the metabolic depressant effect of oligomycin but further suppressed the chemosensory response. These results confirm the above predictions and strengthen the metabolic hypothesis for O-2 chemoreception in the CB.