Carbonic anhydrase and chemoreception in the cat carotid body.
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.
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
R
R
Iturriaga
S
S
Lahiri
A
A
Mokashi
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002344:Carotid Body / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D008704:Methazolamide / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010477:Perfusion
D001639:Bicarbonates; D002245:Carbon Dioxide; D009538:Nicotine; D002256:Carbonic Anhydrases; D008704:Methazolamide