Multimodal Photoswitchable Modulation of Insect Glutamatergic Transmission by Quaternary Ammonium Azobenzenes

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Abstract
Photopharmacology provides superior temporal and spatial resolution for studying the functions of ion channels within neuronal networks. Photomodulated channel blockers, such as azobenzene quaternary ammonium derivatives, QAQ (quaternary ammonium-azobenzene-quaternary ammonium), DENAQ (diethylamine-azobenzene-quaternary ammonium), and AAQ (acrylamide-azobenzene-quaternary ammonium), have been intensively studied in vertebrates, but their effects on insects remain unknown. In this paper we study their ability to modulate synaptic transmission at the neuromuscular junction of Calliphora vicina larvae. Despite having rather similar structures, these compounds cause dramatically different effects. QAQ in its trans-form effectively inhibits excitatory postsynaptic currents by blocking the ion pores of postsynaptic glutamate receptors at micromolar concentrations, but it becomes less effective when photoconverted to cis-form. In contrast, DENAQ behaves as a light-dependent potentiator of synaptic transmission that triggers the appearance of multispike responses, likely due to the blockage of presynaptic potassium channels, which enhances nerve excitability. The effect of AAQ demonstrates complex action due to a combination of these two mechanisms. The same targets for these compounds were previously identified in vertebrates, suggesting significant evolutionary conservativity of the targets. Our study highlights that even for structurally related compounds the targets, mode of action, and light-dependence can vary dramatically. Thus, the rational use of photochromic compounds requires careful analysis of their targets and molecular mechanism(s) of action.
Funding Information
  • IEPhB Research program

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