Investigation of Nasal CO2 Receptor Transduction Mechanisms in Wild-type and GC-D Knockout Mice

The main olfactory system of mice contains a small subset of olfactory sensory neurons (OSNs) that are stimulated by CO2. The objective of this study was to record olfactory receptor responses to a range of CO2 concentrations to further elucidate steps in the proposed CO2 transduction pathway in mice. Electro-olfactograms (EOGs) were recorded before and after inhibiting specific steps in the CO2 transduction pathway with topically applied inhibitors. Inhibition of extracellular carbonic anhydrase (CA) did not significantly affect EOG responses to CO2 but did decrease EOG responses to several control odorants. Inhibition of intracellular CA or cyclic nucleotide-gated channels attenuated EOG responses to CO2, confirming the role of these components in CO2 sensing in mice. We also show that, like canonical OSNs, CO2-sensitive OSNs depend on Ca 2+-activated Cl − channels for depolarization of receptor neurons. Lastly, we found that guanylyl cyclase-D knockout mice were still able to respond to CO2, indicating that other pathways may exist for the detection of low concentrations of nasal CO2. We discuss these findings as they relate to previous studies on CO2-sensitive OSNs in mice and other animals. Key words: carbonic anhydrase, cGMP, chloride channels, CNG channels, olfaction, olfactory sensory neuron