Malenka R C, Madison D V, Nicoll R A
Nature. 1986;321(6066):175-7. doi: 10.1038/321175a0.
Protein kinase C (PKC), a calcium-dependent phospholipid-sensitive kinase which is selectively activated by phorbol esters, is thought to play an important role in several cellular processes. In mammalian brain PKC is present in high concentrations and has been shown to phosphorylate several substrate phosphoproteins, one of which may be involved in the generation of long-term potentiation (LTP), a long-lasting increase in synaptic efficacy evoked by brief, high-frequency stimulation. Since the hippocampus contains one of the brain's highest levels of binding sites for phorbol esters and is the site where LTP has been most thoroughly characterized, we examined the effects of phorbol esters on hippocampal synaptic transmission and LTP. We found that phorbol esters profoundly potentiate excitatory synaptic transmission in the hippocampus in a manner that appears indistinguishable from LTP. Furthermore, after maximal synaptic enhancement by phorbol esters, LTP can no longer be elicited. Although the site of synaptic enhancement during LTP is not clearly established, phorbol esters appear to potentiate synaptic transmission by acting primarily at a presynaptic locus since changes in the postsynaptic responses to the putative transmitter, glutamate, cannot account for the increased synaptic responses induced by phorbol esters. These findings, in conjunction with previous biochemical studies, raise the possibility that, in mammalian brain, PKC plays a role in controlling the release of neurotransmitter and may be involved in the generation of LTP.
蛋白激酶C（PKC）是一种钙依赖性磷脂敏感激酶，可被佛波酯选择性激活，被认为在多种细胞过程中发挥重要作用。在哺乳动物大脑中，PKC浓度很高，并且已被证明可使几种底物磷蛋白磷酸化，其中一种可能参与长时程增强（LTP）的产生，LTP是由短暂的高频刺激引起的突触效能的持久增加。由于海马体含有大脑中佛波酯结合位点的最高水平之一，并且是LTP最彻底特征化的部位，我们研究了佛波酯对海马体突触传递和LTP的影响。我们发现佛波酯以一种与LTP难以区分的方式显著增强海马体中的兴奋性突触传递。此外，在佛波酯使突触增强达到最大值后，LTP就不再能被诱发。尽管LTP期间突触增强的位点尚未明确确定，但佛波酯似乎主要通过作用于突触前位点来增强突触传递，因为对假定递质谷氨酸的突触后反应变化无法解释佛波酯诱导的突触反应增加。这些发现与先前的生化研究相结合，增加了PKC在哺乳动物大脑中控制神经递质释放并可能参与LTP产生的可能性。
