FK506, a Ca2+/calmodulin-dependent phosphatase inhibitor, inhibits the induction of long-term potentiation in the rat hippocampus.

The effects of FK506, a Ca2+/calmodulin-dependent phosphatase 2B (calcineurin) inhibitor, on the synaptic potentials and long-term potentiation (LTP) were investigated, using extracellular recordings in the CA1 region of adult rat hippocampal slices. Bath application of FK506 (1-50 mu M) produced a dose-dependent and reversible inhibition on the field excitatory postsynaptic potentials. FK506 also showed an inhibitory effect on the induction of LTP evoked by theta-burst stimulation. Analyses of the fiber volley and paired-pulse facilitation revealed that FK506-induced effects were based on postsynaptic mechanisms. These results demonstrate that FK506 inhibits both the synaptic transmission and the LTP induction, and suggest that calcineurin plays a promoting role in the LTP processes in the hippocampus of adult rats.