Phorbol diacetate differentially regulates the N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated components of the rat hippocampal excitatory postsynaptic currents.

The effects of phorbol 12,13-diacetate (PDAc) on evoked excitatory transmission were studied in neurons of the CA1 area of hippocampal slices of rats, using whole-cell voltage clamp of pyramidal neurons in situ and stimulation of the Schaffer collaterals. The application of PDAc (10 microM) increased the amplitude of the excitatory postsynaptic current (EPSC) and caused a lengthening of its decay, due to an increase in the contribution of the N-methyl-D-aspartate (NMDA) component to the total EPSC. The latter effect was depend upon the concentration of calcium in the extracellular medium. Experiments in which we separated the two components of the EPSCs by 6-cyano-7-nitroquinoxaline-2,3-dione and by 2-amino-5-phosphonopentanoic acid also demonstrated a more pronounced increase in the NMDA receptor-mediated current under PDAc. The effects of PDAc were markedly attenuated by the extracellular application of the protein kinase C inhibitor H-7 (300 microM), but not by intracellular perfusion with 20 mM of the same drug.