A CALCINEURIN INHIBITOR, FK506, BLOCKS VOLTAGE-GATED CALCIUM CHANNEL-DEPENDENT LTP IN THE HIPPOCAMPUS

The effects of FK506, an immunosuppressant and protein phosphatase 2B (calcineurin) inhibitor, on the voltage-gated calcium channel (VGCC)-d ependent long-term potentiation (LTP) were investigated in the CA1 reg ion of mice hippocampal slices. VGCC-dependent LTP was induced either by a brief application of a potassium channel blocker tetraethyleneanm onium (TEA), or by a strong tetanic stimulation under the blockade of NMDA-receptors. FK506 (1-50 mu M) produced dose-dependent inhibition o n TEA-induced LTP. Cyclosporin A (CysA 50 mu M), another calcineurin i nhibitor, showed a similar inhibitory effect on TEA-induced LTP. FK506 (10 mu M) also blocked the strong tetanus-induced LTP, but had no eff ect on the post-tetanic potentiation. By using a subthreshold weak tet anic stimulation protocol, we also found that low concentration of FK5 06 (1 mu M) produced neither inhibition nor potentiation on VGCC-depen dent LTP. These results showed FK506 and CysA exerted inhibitory effec ts on VGCC-dependent LTP, and suggest that calcineurin is involved in the processes of this kind of synaptic plasticity. (C) 1998 Elsevier S cience Ireland Ltd. All rights reserved.