To test the hypothesis that CO2 and O2 chemoreception in the carotid body (CB) may depend on its
carbonic anhydrase (CA) activity, we used an in vitro cat CB preparation and studied the effects of
methazolamide, a permeable CA inhibitor (pK 7.3), on the chemosensory responses to CO2, O2, and
nicotine. The isolated CB was perfused and superfused with Tyrode
solution, free of CO2-HCO3-, at 36.0 +/- 0.5 degrees C. The frequency of chemosensory discharges was recorded from the whole carotid sinus nerve. The responses to bolus
injections (0.3-0.5 ml) of Tyrode
solution equilibrated with PCO2 of 38-110 Torr, switching from
HEPES to CO2-HCO3- Tyrode (PCO2 = 25-60 Torr) for about 3 min, hypoxic Tyrode (PO2 = 25-30 Torr) for 2-8 min, perfusate flow interruptions for approximately 4 min, and bolus
injections of
nicotine (4 nmol) were studied before, during, and after perfusion (30-45 min) with
methazolamide (42.4 microM).
Methazolamide reversibly inhibited, delayed, and reduced the responses to transient CO2 stimulus, diminished the onset of but not the late response to prolonged CO2 stimulus, and delayed but did not decrease the responses to
hypoxia and perfusate interruption. The response to
nicotine did not change. The results indicated that CA in the glomus cells played a crucial role primarily in the speed and magnitude of the initial response to CO2 stimulus and indirectly influenced O2 chemoreception. These effects were upstream from the
nicotine receptor-mediated sensory response.