PROTEIN-KINASE-C IS REQUIRED FOR LONG-LASTING SYNAPTIC ENHANCEMENT BYTHE NEUROPEPTIDE DRNFLRFAMIDE IN CRAYFISH

The FMRFamide-related neuropeptide AspArgAsnPheLeuArgPhe-NH2 (DRNFLRFa mide, DF2) induces a long-lasting enhancement of synaptic transmission at neuromuscular junctions on the crayfish deep abdominal extensor mu scles. Here we investigated the function of protein kinase C (PKC) in this effect because PKC has been implied in the control of long-term s ynaptic modulation in other systems. The general kinase antagonist sta urosporine reduced both the initial increase in excitatory postsynapti c potential (EPSP) amplitude and the duration of synaptic enhancement. Unlike staurosporine, the selective PKC inhibitors, chelerythrine and bisindolylmaleimide, augmented the initial EPSP increase. However, li ke staurosporine, they also reduced the duration of synaptic enhanceme nt. The PKC activator, phorbol-12-myristate 13-acetate, induced a long -lasting synaptic enhancement that was blocked by chelerythrine. These results show that synaptic enhancement by DF2 is mediated by differen t intracellular signaling systems that act in temporal sequence. The i nitial increase in EPSP amplitudes is negatively regulated by PKC and involves another, staurosporine-sensitive, kinase; whereas, the mainte nance of synaptic enhancement requires PKC.