Abstract
Calcium-permeable and thermosensitive transient receptor potential (TRP) channels mediate the nociceptive transduction of noxious temperature in Drosophila nociceptors. However, the underlying molecular mechanisms are not completely understood. Here we find that Subdued, a calcium-activated chloride channel of the Drosophila anoctamin family, functions in conjunction with the thermo-TRPs in thermal nociception. Genetic analysis with deletion and the RNAi-mediated reduction of subdued show that subdued is required for thermal nociception in nociceptors. Further genetic analysis of subdued mutant and thermo-TRP mutants show that they interact functionally in thermal nociception. We find that Subdued expressed in heterologous cells mediates a strong chloride conductance in the presence of both heat and calcium ions. Therefore, our analysis suggests that Subdued channels may amplify the nociceptive neuronal firing that is initiated by thermo-TRP channels in response to thermal stimuli.
Highlights
Subdued is a calcium-activated chloride channel of the anoctamin family in Drosophila
We find that Subdued, a calcium-activated chloride channel of the Drosophila anoctamin family, functions in conjunction with the thermo-transient receptor potential (TRP) in thermal nociception
Our analysis suggests that Subdued channels may amplify the nociceptive neuronal firing that is initiated by thermo-TRP channels in response to thermal stimuli
Summary
Subdued is a calcium-activated chloride channel of the anoctamin family in Drosophila. We find that Subdued, a calcium-activated chloride channel of the Drosophila anoctamin family, functions in conjunction with the thermo-TRPs in thermal nociception. In Drosophila larvae, class IV multidendritic (md) neurons are sensory nociceptors and mediate behavioral responses to noxious stimuli (4 – 6). Such responses are elicited by chemical irritants [7], noxious high temperatures [6, 7], and mechanical forces [8]. The thermo-TRP subgroup of the ion channels, consisting of Painless and dTRPA1, participates in the transduction of noxious heat stimuli in nociceptive sensory neurons (5, 6, 9 –11). We find that the Subdued channel is required for thermal nociception in collaboration with thermo-TRPs in Drosophila nociceptive behaviors to heat
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