CALCINEURIN INHIBITORS, FK506 AND CYCLOSPORINE-A, SUPPRESS THE NMDA RECEPTOR-MEDIATED POTENTIALS AND LTP, BUT NOT DEPOTENTIATION IN THE RATHIPPOCAMPUS

The effects of FK506, a Ca2+/calmodulin-dependent phosphatase 2B (calc ineurin) inhibitor, on the NMDA receptor-mediated potentials and synap tic plasticity were investigated in the CA1 region of the rat hippocam pus. Bath application of FK506 (50 mu M) produced a 45% inhibition on the NMDA receptor-mediated potentials. FK506 also inhibited tile induc tion of long-term potentiation (LTP), but had no effect on the depoten tiation in the CA1 hippocampus. Cyclosporin A (100 mu M), another calc ineurin inhibitor, mimicked the effects of FK506 on the NMDA responses and synaptic plasticity. These results suggest that FK506 inhibits th e activity of NMDA receptors via the involvement of calcineurin. The d ifferential effects of FK506 on LTP and depotentiation may attribute t o the partial inhibition on the activity of NMDA receptors and the sub sequent attenuation of inh acellular Ca2+ increase.