Carotid body chemoreception: the importance of CO2-HCO3- and carbonic anhydrase. (review).
The current hypotheses of carotid body (CB) chemoreception regard the glomus cells as the initial site of stimulus transduction. The consensus is that the transduction of chemical stimulus is coupled with the release of transmitter(s) from the glomus cells, which in turn generates action potentials in the afferent nerve terminals. Carbonic anhydrase (CA) is present in the glomus cells of the CB. Inhibition of CA activity in the CB in situ reduces the carotid chemosensory responses to CO2 and to O2, suggesting a common mechanism of chemosensing for both stimuli. However, CA inhibitors also block the red blood cell enzyme. Thus, the CO2 hydration reaction does not come to completion within the transit time of the blood from the lung to the CB. A steady-state reaction is not reached until later and so the PCO2 and pH levels in arterial blood samples are not the same as those sensed by the CB. Experiments in vitro using cat CB perfused and superfused with cell-free solutions, which had been pre-equilibrated with respiratory gases, strongly support the proposition that the CA activity in CB cells is essential for the speed and amplitude of the initial response to CO2 and for its subsequent adaptation. The immediate response to hypoxia also is delayed, but the late steady-state was less dependent on CA activity. In the nominal absence of CO2-HCO3- from the perfusate, hypoxic chemoreception persisted and its magnitude is not affected by CA inhibition, except for a delay which may be due to the initial alkaline pH of the glomus cells. Recent experiments performed in isolated glomus cells and in the whole CB show that hypoxia does not modify significantly the intracellular pH. By its simple catalytic function, CA can speed up the approach of the CO2 hydration reaction to equilibrium. However, CA may also contribute in the steady-state to the regulation of pHi by providing a continuous supply of H+ and HCO3-. Furthermore, CA performs a facilitatory role in the physiological chemosensory responses to CO2 and O2 in the presence of extracellular CO2-HCO3-. This role is likely to be related to the ion exchanger function and then to pHi regulation in the chemoreceptor cells.
Iturriaga
R
R
Laboratory of Neurobiology, Catholic University of Chile, Santiago.
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002344:Carotid Body / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002415:Cats; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D008704:Methazolamide / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits; D051381:Rats
D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases; D008704:Methazolamide