A calcineurin inhibitor, FK506, blocks voltage-gated calcium channel-dependent LTP in the hippocampus

Hideharu Onuma, Yun Fei Lu, Kazuhito Tomizawa, Akiyoshi Moriwaki, Masaaki Tokuda, Osamu Hatase, Hideki Matsui

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Abstract

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 μM) produced dose-dependent inhibition on TEA-induced LTP. Cyclosporin A (CysA 50 μM), another calcineurin inhibitor, showed a similar inhibitory effect on TEA-induced LTP. FK506 (10 μM) 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 μM) 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.

Original languageEnglish
Pages (from-to)313-319
Number of pages7
JournalNeuroscience Research
Volume30
Issue number4
DOIs
Publication statusPublished - Apr 1 1998

Keywords

  • Calcineurin
  • Cyclosporin A
  • FK506
  • Hippocampus
  • LTP
  • Voltage-gated calcium channel

ASJC Scopus subject areas

  • Neuroscience(all)

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    Onuma, H., Lu, Y. F., Tomizawa, K., Moriwaki, A., Tokuda, M., Hatase, O., & Matsui, H. (1998). A calcineurin inhibitor, FK506, blocks voltage-gated calcium channel-dependent LTP in the hippocampus. Neuroscience Research, 30(4), 313-319. https://doi.org/10.1016/S0168-0102(98)00012-1