CO2 per se activates carbon dioxide receptors

SUMMARY Carbon dioxide has been used in traps for more than six decades to monitor mosquito populations and help make informed vector management decisions. CO 2 is sensed by gustatory receptors (GRs) housed in neurons in the maxillary palps. CO 2 -sensitive GRs have been identified from the vinegar fly and mosquitoes, but it remains to be resolved whether these receptors respond to CO 2 or bicarbonate. As opposed to the vinegar fly, mosquitoes have three GR subunits, but it is assumed that subunits GR1 and GR3 form functional receptors. In our attempt to identify the chemical species that bind these receptors, we discovered that GR2 and GR3 are essential for receptor function and that GR1 appears to function as a modulator. While Xenopus oocytes coexpressing Culex quinquefasciatus subunits CquiGR1/3 and CquiGR1/2 were not activated, CquiGR2/3 gave robust responses to sodium bicarbonate. Interestingly, CquiGR1/2/3- coexpressing oocytes gave significantly lower responses. That the tertiary combination is markedly less sensitive than the GR2/GR3 combination was also observed with orthologs from the yellow fever and the malaria mosquito. By comparing responses of CquiGR2/CquiGR3- coexpressing oocytes to sodium bicarbonate samples (with or without acidification) and measuring the concentration of aqueous CO 2 , we showed that there is a direct correlation between dissolved CO 2 and receptor response. We then concluded that subunits GR2 and GR3 are essential for these carbon dioxide-sensitive receptors and that they are activated by CO 2 per se, not bicarbonate.