Toxicological effects of gap junction inhibitors on the yellow fever mosquito, Aedes aegypti

Vector borne disease presents a serious threat to human and animal health, and as such, control of these diseases is imperative. In many cases, due to lack of effective treatments, control of the disease mandates control of the mosquito population instead. Aedes aegypti is an important disease vector in itself, as well as a valuable model for other mosquito vector species. This allows us to both directly and indirectly examine novel targets for insecticidal control. Gap junctions are intercellular channels that allow for direct communication between adjacent cells via the movement of certain small molecules and ions. Gap junctions of vertebrates and invertebrates are comprised of evolutionarily distinct groups of proteins known as connexins and innexins respectively, making innexins interesting potential targets. In this study we use pharmacological means to assess the potential of gap junctions as novel targets for insecticide development. We selected three commercially available gap junction inhibitors and assessed their efficacy on the survival and excretory physiology of adult female mosquitoes via direct hemolymph injections and/or topical application to the cuticle. In addition, we added the inhibitors to the rearing water of larvae to assess their larvicidal activity. We found that the inhibitors incapacitated and killed adult and larval mosquitoes in a dose dependent manner and caused a reduction in adult female excretory output, which suggests that gap junctions may offer valuable physiological targets to exploit for insecticide development. Supported by a Ohio Mosquito Control Association grant to TLC and a NIH R03 grant to PMP.