PHORBOL ESTERS ENHANCE SYNAPTIC TRANSMISSION BY A PRESYNAPTIC, CALCIUM-DEPENDENT MECHANISM IN RAT HIPPOCAMPUS

1. The effects of phorbol esters on evoked and spontaneous excitatory neurotransmission were studied in the CA1 area in the in vitro hippoca mpal slice preparation of the rat. Experiments were conducted using fi eld potential recording and whole-cell voltage clamp of CA1 pyramidal neurons. 2. Pyramidal cells dialysed during whole-cell recording with EGTA-containing electrode solutions, unable to support the induction o f long-term potentiation (LTP), still showed robust phorbol ester-indu ced potentiation of excitatory synaptic transmission. 3. Spontaneous m iniature excitatory postsynaptic currents (EPSCs), recorded in whole-c ell voltage clamp in the presence of tetrodotoxin and picrotoxin, had amplitudes ranging from 4 to 40 pA and occurred at an average frequenc y of 0.8-5 Hz. Neither the amplitude nor the frequency of spontaneous EPSCs was altered by cadmium, dihydropyridines, or omega-conotoxin GVI A. 4. The phorbol ester 4-beta-phorbol 12,13-diacetate increased the f requency of spontaneous miniature EPSCs without changing the shape of the EPSC amplitude distribution, suggesting that phorbol esters exert their potentiating effects presynaptically. 5. Blockade of voltage-dep endent calcium channels with cadmium attenuated the phorbol-induced in crease in spontaneous miniature EPSCs frequency. The phorbol ester-ind uced increase in miniature EPSC frequency was also attenuated by dihyd ropyridines, but not by omega-conotoxin GVIA. 6. Unlike spontaneous sy naptic currents, stimulus-evoked synaptic currents were reduced by ome ga-conotoxin but not by nifedipine. 7. We conclude that the phorbol es ter increases spontaneous release of glutamate by modulating an L-type channel that does not participate in stimulus-evoked neurotransmitter release.