The mechanism of block of glutamate synapses by dipicolinic acid

Abstract

The effect of dipicolinic acid (2,6-pyridine dicarboxylic acid) on the mealworm neurornuscular junction was studied using conventional microelectrode recording techniques. Dipicolinic acid (10-5-10-3 M) added to the bathing solution reversibly blocked neuromuscular transmission. The depolarization in response to iontophoretically applied L-glutamate (glutamate potential) was not affected by dipicolinic acid even when the neurally evoked excitatory postsynaptic potential (EPSP) was totally abolished. Focal extracellular recordings from single synaptic sites revealed that in the presence of 1 x M dipicolinic acid the presynaptic spike was unchanged, but the quanta1 content for evoked transmitter release was reduced. The calcium-dependent action potential elicited by direct stimulation of the muscle fiber was not impaired by dipicolinic acid. These results suggest that dipicolinic acid interferes with the transmitter-releasing mechanism from the presynaptic terminal.