Inhibition of Glutamate Carboxypeptidase II Regulates Synaptic Transmission in the Crayfish Neuromuscular Junction

Abstract

Glutamate carboxypeptidase II (GCP II) is a glial ectoenzyme known to hydrolyze N-Acetylaspartylglutamate (NAAG), one of the most abundant and widely distributed neurotransmitters in the mammalian nervous system. It has been proposed that NAAG is linked to various conditions such as schizophrenia, ALS and diabetic neuropathy. However, the role of NAAG and other glutamatergic peptides at the crayfish neuromuscular junction has not been investigated. By introducing the GCP II inhibitor ZJ-43, we sought to further elucidate the mechanism by which GCPII regulates the synapse. To determine the effects of GCP II, we compared excitatory postsynaptic potential (EPSP) amplitudes of the control experiments and the experiments with the ZJ-43 treatments. We used the method of paired pulse stimulation to determine whether the effect was occurring in the postynapse or presynapse. In addition, we used low frequency and high frequency stimulation. Our results suggest that the inhibition of GCPII decreases the amplitude of the EPSP during both high and low frequency stimulation through mechanisms in either the presynapse or both the presynapse and postsynapse.