The role of
carbonic anhydrase (CNA) in the dynamics of carotid body (CB) function was tested by studying the effects of the membrane-permeable CNA inhibitor
methazolamide on the chemosensory responses of the cat CB, perfused and superfused in vitro with cell-free and modified Tyrode
solution at 36.5 +/- 0.5 degrees C in the presence of CO2-HCO3- (PO2 = 120 Torr, PCO2 = 32 Torr, pH = 7.40). The bulk of CO2 flow to the CB from the external milieu was overwhelmingly large relative to the metabolic production of CO2 in the CB. Accordingly, the relative contribution of the endogenous CO2 to the CB responses was small. The chemosensory nerve discharges were recorded from the whole desheathed carotid sinus nerve. The responses to acidic
hypercapnia (PCO2 = 50-60 Torr, pH = 7.20-7.10),
hypoxia (PO2 = 25 and 50 Torr), perfusate flow interruption, and bolus
injections of
sodium cyanide (20-40 nmol) were tested. To contrast, we also measured the effects of
nicotine (2-4 nmol), which may act at sites other than those for O2 and CO2.
Methazolamide (30 mg/l) in the perfusate at constant PCO2 and pH reduced the baseline activity and delayed the responses to step changes in PCO2 (and concomitantly pH) and PO2 and to
cyanide but not to
nicotine. The steady-state responses to these stimuli, measured as differences from control, were reduced, but not significantly. The initial overshoots seen with step changes in both high PCO2 and low PO2 were eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)