Bortolotto Z A, Collingridge G L
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK.
Eur J Neurosci. 2000 Nov;12(11):4055-62. doi: 10.1046/j.1460-9568.2000.00291.x.
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 Gö 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.
蛋白激酶C（PKC）参与海马体CA1突触处N-甲基-D-天冬氨酸（NMDA）受体依赖性长时程增强（LTP）的诱导这一可能性，一直是大量研究的主题。然而，许多结论是通过使用相对非特异性的PKC抑制剂得出的。在本研究中，我们研究了PKC在成年大鼠海马体切片中破伤风诱导的AMPA受体介导的突触传递长时程增强中的作用。特别是，我们研究了PKC在由促代谢型谷氨酸受体的突触激活触发并调节长时程增强诱导的分子开关过程中的可能作用。我们发现，所检测的三种PKC抑制剂，白屈菜红碱、Ro-31-8220和Gö 6983，在与抑制PKC一致的浓度下均阻断分子开关的设置。相比之下，这些抑制剂即使以高得多的浓度应用，对长时程增强的诱导也没有影响。一种蛋白激酶A（PKA）抑制剂Rp-cAMPS对这两个过程均无影响。我们认为，在这个突触处诱导长时程增强既不需要PKC也不需要PKA。然而，PKC通过分子开关过程参与长时程增强诱导的调节。
