Fig. 1.

(A) In the mouse system, CO₂ diffuses into the CO₂ receptor neurons. Its hydration is catalyzed by the carbonic anhydrase CAII to form carbonic acid, which immediately dissociates to form protons and bicarbonate. The bicarbonate activates the receptor guanylate cyclase GC-D, which converts bound GTP to cGMP. The cGMP then binds to the cyclic nucleotide gated channel CNGA3 and causes it to open and permit the entry of calcium ions that initiate action potentials that travel to the necklace glomeruli in the olfactory bulb. The response to CO₂ is then terminated when PDE2A converts the cGMP into GMP. (B) Nematodes employ a remarkably similar system for CO2 detection. The carbonic anhydrase CAH-2 produces the bicarbonate that is detected by GCY-9. GCY-9 produces the cGMP that activates the TAX-2/TAX-4 CNG channel. The role of a PDE in terminating the nematode response to CO₂ has not yet been confirmed. (C) In fruit flies, a role for carbonic anhydrase in CO₂ detection is likely but not yet confirmed. In low CO₂, the GR21a and GR63a gustatory receptors are required, but in high CO₂, the ionotropic receptors IR64a and IR8a work together to detect a drop in sensory lymph pH.