Functional and pharmacological characterization of antennal sodium channels from Aedes aegypti

Voltage-gated sodium channels are essential for the electrical signaling in the insect nervous system. It is well-established that most insect species rely on alternative splicing and RNA editing of a single sodium channel gene to generate functional diversity of sodium channels. However, little is known on the role of tissue-specific alternative splicing and RNA editing in insect neurophysiology and neurotoxicology. Insect antennae are major sensory organs for detecting environmental stimuli. In this study, using the Xenopus oocyte system we functionally and pharmacologically characterized 11 sodium channel variants isolated from antennae of Aedes aegypti, a major vector of human diseases. The 11 variants belong to 11 different splice types. Some of the variants possess 1 to 2 RNA editing sites which are also found in sodium channel clones from antennae of Aedes albopicus. We found that these antennal sodium channels vary significantly in their voltage dependence of both activation and inactivation. Furthermore, we observed differential sensitivity of the antennal sodium channels to transfluthrin, a volatile pyrethroid insecticide that elicits spatial repellency in Ae. aegypti solely by activating sodium channels. The observed differences in channel gating and sensitivity to transfluthrin are likely due to the presence of unique RNA editing sites and/or different usages of alternative exons. Identification of unique alternative spliced/RNA-edited sodium channel variants in mosquito antennae provide an important foundation for elucidating the role of sodium channels in modulating sensory physiology in human disease vectors.