Wikström Martin A, Matthews Paul, Roberts Dewi, Collingridge Graham L, Bortolotto Zuner A
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Neuropharmacology. 2003 Nov;45(6):828-36. doi: 10.1016/s0028-3908(03)00336-8.
To identify the enzymes involved in the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at CA1 synapses of two-week-old rats we have tested various kinase inhibitors. Surprisingly, given the large body of evidence supporting a role for calcium/calmodulin-dependent protein kinase II (CaMKII) in LTP, inhibition of this enzyme did not affect the induction of LTP at this age. Similarly inhibition of protein kinase A (PKA) or protein kinase C (PKC) was also without effect. However, inhibition of CaMKII together with inhibition of either PKA or PKC fully blocked the induction of LTP. These experiments reveal, unexpectedly, the existence of two parallel kinase pathways, one involving CaMKII and the other PKA and PKC, either of which can fully support the induction of LTP, at this stage of development.
为了确定参与两周龄大鼠CA1突触处N-甲基-D-天冬氨酸（NMDA）受体依赖性长时程增强（LTP）诱导的酶，我们测试了各种激酶抑制剂。令人惊讶的是，尽管有大量证据支持钙/钙调蛋白依赖性蛋白激酶II（CaMKII）在LTP中起作用，但抑制这种酶并不影响该年龄阶段LTP的诱导。同样，抑制蛋白激酶A（PKA）或蛋白激酶C（PKC）也没有效果。然而，抑制CaMKII并同时抑制PKA或PKC则完全阻断了LTP的诱导。这些实验意外地揭示，在发育的这个阶段，存在两条平行的激酶途径，一条涉及CaMKII，另一条涉及PKA和PKC，其中任何一条都可以完全支持LTP的诱导。
