POTENTIATION OF SPONTANEOUS ACETYLCHOLINE-RELEASE FROM MOTOR-NERVE TERMINALS BY GLUTAMATE IN XENOPUS TADPOLES

Extracellular application of glutamate (100 mu M) increased the sponta neous secretion of acetylcholine, as well as the amplitude and decay t ime of miniature endplate potentials at developing neuromuscular synap ses in Xenopus tadpoles. Kainate, quisqualate and N-methyl-D-aspartate (100 mu M each) increased miniature endplate potential frequency by 2 6-, 13- and four-fold, respectively. The rank order of efficacy at 100 mu M was kainate > quisqualate > N-methyl-D-aspartate > glutamate. Th e effect of kainate on miniature endplate potential frequency was inhi bited by 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (20 mu M), but not b y (+/-)-2-amino-5-phosphonovalerate (20 mu M). Treatment with the volt age-dependent Ca2+ channel blockers verapamil (10 mu M), Cd2+ (100 mu M) or omega-conotoxin (1 mu M) inhibited the potentiating action of ka inate on miniature endplate potential frequency. On the other hand, 1S ,3R-1-aminocyclopentane-1,3-dicarboxylate (300 mu M), a glutamate meta botropic receptor agonist, inhibited the spontaneous acetylcholine rel ease, which was antagonized by the application of 2-amino-3-phosphonop ropionate (500 mu M). The potentiating effect of glutamate receptor ag onists on the miniature endplate potential frequency declined or disap peared in older Xenopus tadpoles. Quisqualate (100 mu M) and N-methyl- D-aspartate (100 mu M) but not kainate (30 mu M) increased the amplitu de and decay time of miniature endplate potential, whereas 1S,3R-1-ami nocyciopentane-1,3-dicarboxy]ate (300 mu M) only increased the decay t ime of miniature endplate potentials. These results suggest that there are kainate/quisqualate and N-methyl-D-aspartate receptors existing i n the motor nerve terminals of younger Xenopus tadpoles and the activa tion of these receptors potentiates spontaneous acetylcholine release through increasing Ca2+ influx. Our data suggest that the presynaptic glutamate receptors on cholinergic terminals may be involved in feedba ck regulation of acetylcholine secretion at earlier embryonic stages. Copyright (C) 1996 IBRO.