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)-dependent long-term potentiation (LTP) were investigated in the CA1 region of mice hippocampal slices. VGCC-dependent LTP was induced either by a brief application of a potassium channel blocker tetraethyleneanmonium (TEA), or by a strong tetanic stimulation under the blockade of NMDA-receptors. FK506 (1-50 microM) produced dose-dependent inhibition on TEA-induced LTP. Cyclosporin A (CysA 50 microM), another calcineurin inhibitor, showed a similar inhibitory effect on TEA-induced LTP. FK506 (10 microM) also blocked the strong tetanus-induced LTP, but had no effect on the post-tetanic potentiation. By using a subthreshold weak tetanic stimulation protocol, we also found that low concentration of FK506 (1 microM) produced neither inhibition nor potentiation on VGCC-dependent LTP. These results showed FK506 and CysA exerted inhibitory effects on VGCC-dependent LTP, and suggest that calcineurin is involved in the processes of this kind of synaptic plasticity.
Onuma
H
H
First Department of Physiology, Okayama University Medical School, Japan.
Lu
Y F
YF
Tomizawa
K
K
Moriwaki
A
A
Tokuda
M
M
Hatase
O
O
Matsui
H
H
D000818:Animals; D065095:Calcineurin Inhibitors; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009543:Nifedipine / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007166:Immunosuppressive Agents; D019789:Tetraethylammonium; D016572:Cyclosporine; D009543:Nifedipine; D016559:Tacrolimus