POTENTIATION OF NEUROTRANSMITTER RELEASE BY ACTIVATION OF PRESYNAPTICGLUTAMATE RECEPTORS AT DEVELOPING NEUROMUSCULAR SYNAPSES OF XENOPUS

1. Glutamate receptors play important roles in synaptic plasticity and neural development. Here we report that, at the developing neuromuscu lar synapses in Xenopus cultures, the activation of presynaptic glutam ate receptors at motor nerve terminals potentiates spontaneous acetylc holine (ACh) release. 2. Co-cultures of spinal neurons and myotomal mu scle cells were prepared from 1-day-old Xenopus embryos. Spontaneous s ynaptic currents (SSCs) were recorded from innervated myocytes using w hole-cell recording. Bath application of glutamate (10 mu M) markedly increased the frequency of SSCs, and the action of glutamate was rever sible. 3. Pretreatment with 0.3 mu M tetrodotoxin, which blocks Na+ ch annels and the conduction of action potentials, only slightly inhibite d the potentiating action of glutamate on SSCs. Furthermore, the enhan cement of ACh secretion was much more prominent when glutamate was app lied locally to the synaptic region. 4. Three types of glutamate recep tor agonists, kainate, quisqualate, AMPA (alpha-amino-3-hydroxy-5-meth yl-4-isoxazole propionic acid) and NMDA (N-methyl-D-aspartate), were e ffective in inducing the potentiating effect. The ranking order was: g lutamate > kainate > NMDA > AMPA > quisqualate. Glycine potentiated th e effects induced by NMDA. Metabotropic receptors were not involved in the potentiating action of glutamate. 5. The potentiating effect of g lutamate depended on the influx of Ca2+ through both L-type Ca2+ chann els and NMDA-gated channels. 6. Since glutamate is known to be co-rele ased with ACh at some cholinergic nerve terminals, the released glutam ate may serve as a positive feedback regulation of ACh secretion at de veloping neuromuscular junctions via its action on presynaptic glutama te receptors.