TRP Channels in Insect Stretch Receptors as Insecticide Targets

Abstract

Defining the molecular targets of insecticides is crucial for assessing their selectivity and potential impact on environment and health. Two commercial insecticides are now shown to target a transient receptor potential (TRP) ion channel complex that is unique to insect stretch receptor cells. Pymetrozine and pyrifluquinazon disturbed Drosophila coordination and hearing by acting on chordotonal stretch receptor neurons. This action required the two TRPs Nanchung (Nan) and Inactive (Iav), which co-occur exclusively within these cells. Nan and Iav together sufficed to confer cellular insecticide responses in vivo and in vitro, and the two insecticides were identified as specific agonists of Nan-Iav complexes that, by promoting cellular calcium influx, silence the stretch receptor cells. This establishes TRPs as insecticide targets and defines specific agonists of insect TRPs. It also shows that TRPs can render insecticides cell-type selective and puts forward TRP targets to reduce side effects on non-target species.

Insect TRP channels as targets for insecticides and repellents

“…As a transducer for sound, gravity and wind, the fly Johnston's organ is one of the most complex chordotonal organs, with five subsets of chordotonal neurons variously specialized to sense vibrations of different frequencies as well as static deflections due to wind and gravity. 50) Although the mechanisms of mechanotransduction in the various classes of Johnston's organ neurons are not clear, heteromeric Nan-Iav TRPV channels are required for the nerve response to mechanical stimulation in all of them, 32) and activation of these channels by pymetrozine and pyrifluquinazon activates Ca 2+ signals in all Johnston's organ neurons as well as in the larval pentascolopidial neurons, 48) affirming the conclusion 55) that all chordotonal organs are affected by pymetrozine.…”

“…Insects have two TRPV channel subunits, Nanchung (Nan) and Inactive (Iav), which, in Drosophila, are co-expressed only in chordotonal neurons, where they form heteromers that are activated by the pyridine azomethine derivative insecticides pymetrozine and pyrifluquinazon. 48) Chordotonal organs are stretch receptors that occur in most joints in the body and are activated by stretch resulting from the relative movement of the articulating joint members. 49) In most joints, chordotonal organs report on joint angle and movement, providing the proprioceptive sense, but a chordotonal organ in the joint between the second and third antennal segments in flies, known as Johnston's organ, reports on movement of the antenna under the influence of gravity, wind and sound, so is involved in the senses of equilibrium, air movement and hearing.…”

“…55) This conclusion is further supported by the observations that pymetrozine also acts selectively on chordotonal organs of the bush cricket tympanum, 56) on Johnston's organ of adult Drosophila and on the pentascolopidial chordotonal organ of Drosophila larvae. 48) Chordotonal organ neurons are specialized according to their function. As a transducer for sound, gravity and wind, the fly Johnston's organ is one of the most complex chordotonal organs, with five subsets of chordotonal neurons variously specialized to sense vibrations of different frequencies as well as static deflections due to wind and gravity.…”

“…Iav is expressed without Nan in motor neurons, where it acts as a key regulator of synaptic develop- ment and function by influencing presynaptic resting Ca 2+ concentration. 60) Nan is expressed in some multidendritic neurons of fly larvae 48) and in a class of sensory hairs on the third antennal segment of Drosophila that respond to dry air, and Nan is required for avoidance of dry air. 46) Because Nan and Iav do not seem to form functional homomers, 48) they might be expected to form functional heteromers with other partners in the other cells where they occur, but this has not been shown.…”

“…60) Nan is expressed in some multidendritic neurons of fly larvae 48) and in a class of sensory hairs on the third antennal segment of Drosophila that respond to dry air, and Nan is required for avoidance of dry air. 46) Because Nan and Iav do not seem to form functional homomers, 48) they might be expected to form functional heteromers with other partners in the other cells where they occur, but this has not been shown. Nevertheless, pymetrozine or pyrifluquinazon only evoked calcium signals in chordotonal neurons and not in larval multidendritic neurons or adult hygroreceptors that only express nan.…”