PRESYNAPTIC ENHANCEMENT OF INHIBITORY SYNAPTIC TRANSMISSION BY PROTEIN KINASE-A AND KINASE-C IN THE RAT HIPPOCAMPUS IN-VITRO

The protein kinase C activator phorbol 12,13-dibutyrate (0.5 mu M PDBu ) and the protein kinase A activator forskolin (20 mu M) each increase d evoked monosynaptic inhibitory postsynaptic current (IPSC) amplitude , without affecting its reversal potential, and increased the frequenc y of miniature IPSCs (mlPSCs), without affecting their amplitude or ki netics, as assessed with whole-cell recording from CA3 pyramidal cells in hippocampal slice cultures. The effects of forskolin and PDBu on b oth evoked IPSC amplitude and mlPSC frequency were additive and were a ntagonized by inhibitors of protein kinases A and C, respectively. The kinase activator-induced increases in mlPSC frequency were quantitati vely comparable to the increases in evoked IPSC amplitude. The increas es in mlPSC frequency were not attenuated by the voltage-dependent cal cium channel blocker Cd2+ (100 mu M). We conclude that stimulation of protein kinases A and C potentiates hippocampal inhibitory synaptic tr ansmission through independent presynaptic mechanisms of action. Kinas e-induced potentiation of spontaneous release does not require modulat ion of axon terminal Ca2+ channels. This mechanism may also contribute substantially to the potentiation of evoked release.