A role for protein kinase C in a form of metaplasticity that regulates the induction of long-term potentiation at CA1 synapses of the adult rat hippocampus
A role for protein kinase C in a form of metaplasticity that regulates the induction of long-term potentiation at CA1 synapses of the adult rat hippocampus
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DOI：
10.1046/j.1460-9568.2000.00291.x
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发表时间：
2000-11-01
影响因子：
3.4
通讯作者：
Collingridge, GL
中科院分区：
文献类型：
--
作者：
Bortolotto, ZA;Collingridge, GL
蛋白激酶C（PKC）参与海马CA 1区突触N-甲基-D-天冬氨酸（NMDA）受体依赖性长时程增强（LTP）的诱导的可能性已成为大量研究的主题。然而，许多结论是从使用相对非特异性的PKC抑制剂中得出的。在本研究中，我们已经研究了PKC在破伤风诱导的LTP的AMPA受体介导的突触传递的成年大鼠海马脑片中的作用。特别是，我们已经研究了PKC在分子开关过程中的可能作用，该过程由亲代谢型谷氨酸受体的突触激活触发并调节LTP的诱导。我们发现，检查的三种PKC抑制剂，白屈菜红碱，Ro-31-8220和Go 6983，在与PKC抑制一致的浓度下都阻断了分子开关的设置。相反，这些抑制剂对LTP的诱导没有影响，即使在非常高的浓度下应用。PKA抑制剂Rp-cAMPS对这两个过程都没有影响。我们认为，无论是PKC还是PKA是必需的，以诱导LTP在这个突触。然而，PKC通过分子开关过程参与LTP诱导的调节。
The possibility that protein kinase C (PKC) is involved in the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at CA1 synapses in the hippocampus has been the subject of considerable investigation. However, many of the conclusions have been drawn from the use of relatively nonspecific PKC inhibitors. In the present study we have examined the role of PKC in tetanus-induced LTP of AMPA receptor-mediated synaptic transmission in hippocampal slices obtained from adult rats. In particular, we have investigated the possible role of PKC in a molecular switch process that is triggered by the synaptic activation of metabotropic glutamate receptors and regulates the induction of LTP. We find that the three PKC inhibitors examined, chelerythrine, Ro-31-8220 and Go 6983, all block the setting of the molecular switch at concentrations consistent with inhibition of PKC. In contrast, these inhibitors are without affect on the induction of LTP, even when applied in very much higher concentrations. A PKA inhibitor, Rp-cAMPS, had no effect on either process. We suggest that neither PKC nor PKA is required to induce LTP at this synapse. However, PKC is involved in the regulation of LTP induction, via the molecular switch process.