Powell C M, Johnston D, Sweatt J D
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
J Biol Chem. 1994 Nov 11;269(45):27958-63.
In area CA1 of the hippocampus, the induction of long term potentiation (LTP) requires activation of either N-methyl-D-aspartate receptors (NMDA receptor-dependent LTP) or voltage-gated Ca2+ channels (NMDA receptor-independent LTP). We have investigated biochemical sequelae of NMDA receptor-independent LTP induction. We find that a persistent increase in second messenger-independent protein kinase C activity is associated with the maintenance phase of NMDA receptor-independent LTP. This increase in protein kinase C activity is prevented by blocking LTP with nifedipine, a Ca2+ channel antagonist, or kynurenic acid, a nonselective glutamate receptor antagonist. Additionally, we find an increase in the catalytic fragment of protein kinase C (PKM) in the maintenance phase of NMDA receptor-independent LTP, indicating that proteolytic activation of protein kinase C may account for its autonomous activation. This increase in the catalytic fragment of protein kinase C is also prevented by blocking LTP induction. These results are the first to demonstrate that persistent protein kinase C activation is a possible mechanism for the maintenance of NMDA receptor-independent LTP.
在海马体的CA1区域，长时程增强（LTP）的诱导需要激活N-甲基-D-天冬氨酸受体（NMDA受体依赖性LTP）或电压门控Ca2+通道（NMDA受体非依赖性LTP）。我们研究了NMDA受体非依赖性LTP诱导的生化后遗症。我们发现，不依赖第二信使的蛋白激酶C活性持续增加与NMDA受体非依赖性LTP的维持阶段相关。用Ca2+通道拮抗剂硝苯地平或非选择性谷氨酸受体拮抗剂犬尿氨酸阻断LTP可防止蛋白激酶C活性的这种增加。此外，我们发现在NMDA受体非依赖性LTP的维持阶段，蛋白激酶C（PKM）的催化片段增加，这表明蛋白激酶C的蛋白水解激活可能是其自主激活的原因。通过阻断LTP诱导也可防止蛋白激酶C催化片段的这种增加。这些结果首次证明，持续的蛋白激酶C激活是维持NMDA受体非依赖性LTP的一种可能机制。
