Heat activation desensitizes Aedes aegypti transient receptor potential ankyrin 1 (AaTRPA1) to chemical agonists that repel mosquitoes

Mosquito transient receptor potential ankyrin 1 (TRPA1) channels are nociceptors that can be activated by noxious heat and/or chemicals (e.g., electrophiles). When activated, TRPA1 channels typically trigger avoidance behaviors. Previous studies have found that mosquito TRPA1 channels play important roles in host-seeking, preferred temperature selection, and avoidance of noxious heat and chemicals in the environment. Accordingly, TRPA1 channels are considered valuable biochemical targets for developing mosquito repellents and/or antifeedants. However, it is presently unknown whether heat activation of mosquito TRPA1 channels impacts their activation by chemical agonists that repel mosquitoes, such as catnip oil and citronellal. To address this gap in knowledge, we heterologously expressed Aedes aegypti TRPA1 (AaTRPA1) in Xenopus laevis oocytes and evaluated its electrophysiological responses to chemical agonists in the presence or absence of a heat stimulus. We found that when AaTRPA1 was heat activated it exhibited dampened electrophysiological responses to either catnip oil or citronellal. Subsequent airborne repellency bioassays with adult female Ae. aegypti revealed that mosquitoes were less repelled by either catnip oil or citronellal when exposed to an increase of ambient temperature that exceeded the heat activation threshold for AaTRPA1 (i.e., >32 °C); in contrast, the repellency of DEET (a non-TRPA1 agonist) was unaffected. Our results suggest that TRPA1-agonizing repellents may offer less protection from mosquitoes when ambient temperatures exceed the thermal activation threshold of mosquito TRPA1 channels. This may have important implications for the choice of mosquito repellents used during extreme heat events, which are becoming more common because of global climate change.