Hussain Rifat J, Carpenter David O
Institute for Health and the Environment, School of Public Health, University at Albany, One University Place, B242, Rensselaer, NY 12144, USA.
Brain Res. 2003 Nov 14;990(1-2):28-37. doi: 10.1016/s0006-8993(03)03381-x.
The effects of three protein kinase C (PKC) agonists (phorbol ester, ingenol and indolactam-V) and two PKC antagonists (D-erythro-sphingosine and chelerythrine) on input-output (I-O) relations in the Schaffer collateral pathway to CA1 (SC-CA1) and mossy fiber pathway to CA3 (MF-CA3) were determined in rat hippocampus brain slices. In the SC-CA1 pathway, phorbol esters and indolactam-V had only small effects on field excitatory post-synaptic potentials (fEPSP) in slices from 60-day animals, although ingenol, an activator of novel PKC isozymes, caused a significant decrease of the field excitatory post-synaptic potentials amplitude in 60-day animals, but not in 30-day animals. In contrast, in the MF-CA3 pathway, PKC agonists induced a significant increase in the field excitatory post-synaptic potentials. PKC antagonists depressed the field excitatory post-synaptic potentials in the SC-CA1 pathway, but had no significant effect in the MF-CA3 pathway. In the MF-CA3 pathway, paired-pulse facilitation was abolished by PKC agonists and unaffected by antagonists. In SC-CA1, it was depressed by agonists to levels below control, whereas it was significantly increased by chelerythine. We conclude that PKC plays important but different roles in both regions. In the SC-CA1 pathway, PKC is almost maximally active under control circumstances, and PKC antagonists significantly reduce synaptic responses. In contrast, in the MF-CA3 pathway, there is no apparent activation under resting circumstances, but significant potentiation of synaptic transmission is induced when PKC is activated. There are developmental changes in the pattern of PKC isozymes, and both pre- and post-synaptic actions are important.
在大鼠海马脑片中，测定了三种蛋白激酶C（PKC）激动剂（佛波酯、大戟醇和吲哚酰胺-V）和两种PKC拮抗剂（D-赤藓鞘氨醇和白屈菜红碱）对至CA1区的Schaffer侧支通路（SC-CA1）和至CA3区的苔藓纤维通路（MF-CA3）中输入-输出（I-O）关系的影响。在SC-CA1通路中，佛波酯和吲哚酰胺-V对60日龄动物脑片中的场兴奋性突触后电位（fEPSP）影响较小，尽管新型PKC同工酶的激活剂大戟醇可使60日龄动物的场兴奋性突触后电位幅度显著降低，但对30日龄动物无此作用。相反，在MF-CA3通路中，PKC激动剂可使场兴奋性突触后电位显著增加。PKC拮抗剂可抑制SC-CA1通路中的场兴奋性突触后电位，但对MF-CA3通路无显著影响。在MF-CA3通路中，PKC激动剂可消除双脉冲易化，而拮抗剂则无此作用。在SC-CA1通路中，激动剂可将双脉冲易化降低至对照水平以下，而白屈菜红碱则可使其显著增加。我们得出结论，PKC在这两个区域发挥着重要但不同的作用。在SC-CA1通路中，PKC在对照情况下几乎处于最大活性状态，PKC拮抗剂可显著降低突触反应。相反，在MF-CA3通路中，静息情况下无明显激活，但PKC激活时可诱导突触传递显著增强。PKC同工酶模式存在发育变化，突触前和突触后作用均很重要。
