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

doi:10.1016/S0168-0102(98)00012-1

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

Graduate School of Medicine Dentistry and Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

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 language	English
Pages (from-to)	313-319
Number of pages	7
Journal	Neuroscience Research
Volume	30
Issue number	4
DOIs	https://doi.org/10.1016/S0168-0102(98)00012-1
Publication status	Published - Apr 1 1998

Keywords

Calcineurin
Cyclosporin A
FK506
Hippocampus
LTP
Voltage-gated calcium channel

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/S0168-0102(98)00012-1

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

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.",

keywords = "Calcineurin, Cyclosporin A, FK506, Hippocampus, LTP, Voltage-gated calcium channel",

author = "Hideharu Onuma and Lu, {Yun Fei} and Kazuhito Tomizawa and Akiyoshi Moriwaki and Masaaki Tokuda and Osamu Hatase and Hideki Matsui",

note = "Funding Information: This study was supported by a Grant-in-Aid for Science Research from Ministry of Education, Science, Sports and Culture of Japan and a research grant from Toyota Physical and Chemical Research Institute.",

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T1 - A calcineurin inhibitor, FK506, blocks voltage-gated calcium channel-dependent LTP in the hippocampus

AU - Onuma, Hideharu

AU - Lu, Yun Fei

AU - Tomizawa, Kazuhito

AU - Moriwaki, Akiyoshi

AU - Tokuda, Masaaki

AU - Hatase, Osamu

AU - Matsui, Hideki

N1 - Funding Information: This study was supported by a Grant-in-Aid for Science Research from Ministry of Education, Science, Sports and Culture of Japan and a research grant from Toyota Physical and Chemical Research Institute.

PY - 1998/4/1

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N2 - 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.

AB - 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.

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KW - Cyclosporin A

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KW - Hippocampus

KW - LTP

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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