Furthering pharmacological and physiological assessment of the glutamatergic receptors at the Drosophila neuromuscular junction

Abstract

Drosophila melanogaster larval neuromuscular junctions (NMJs) serve as a model for synaptic physiology. The molecular sequences of the postsynaptic glutamate receptors have been described; however, the pharmacological profile has not been fully elucidated. The postsynaptic molecular sequence suggests a novel glutamate receptor subtype. Kainate does not depolarize the muscle, but dampens evoked EPSP amplitudes. Quantal responses show a decreased amplitude and area under the voltage curve indicative of reduced postsynaptic receptor sensitivity to glutamate transmission. ATPA, a kainate receptor agonist, did not mimic kainate's action. The metabotropic glutamate receptor agonist t-ACPD had no effect. Domoic acid, a kainate/AMPA receptor agonist, blocks the postsynaptic receptors without depolarizing the muscle. However, SYM 2081, a kainate receptor agonist, did depolarize the muscle and reduce the EPSP amplitude at 1 mM but not at 0.1 mM. This supports the notion that these are generally a quisqualate subtype receptors with some oddities in the pharmacological profile. The results suggest a direct postsynaptic action of kainate due to partial antagonist action on the quisqualate receptors. There does not appear to be presynaptic auto-regulation via a kainate receptor subtype or a metabotropic auto-receptor. This study aids in furthering the pharmokinetic profiling and specificity of the receptor subtypes.