ENHANCEMENT OF AMPA-MEDIATED SYNAPTIC TRANSMISSION BY THE PROTEIN PHOSPHATASE INHIBITOR CALYCULIN-A IN RAT HIPPOCAMPAL SLICES

Using the phosphatase inhibitor calyculin A, we have examined the infl uence of phosphorylation on synaptic transmission and plasticity in ra t CA1 hippocampal slices. Bath application of 0.5 - 1 muM of calyculin A resulted in an increase of 42.6 +/- 2.9% in synaptic responses. The effect produced by calyculin A was not accompanied by changes in fibr e volley, was not associated with changes in paired-pulse facilitation , and could be reproduced by intracellular injection of the compound, thereby indicating a postsynaptic action. Also, the synaptic enhanceme nt produced by calyculin A was expressed only by potentials mediated b y amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not by the NMDA responses recorded in the presence of the AMPA re ceptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and low magnesium. The effect of calyculin A could be prevented by KN-62, an i nhibitor of calcium/calmodulin-dependent protein kinase II. Long-term potentiation could still be induced in the presence of calyculin A, bu t the effect of the compound was slightly reduced on potentiated compa red with control pathways. These results indicate that calyculin A can selectively increase the efficacy of AMPA receptor-mediated synaptic transmission at excitatory synapses.