Wu Jianqun, Rowan Michael J, Anwyl Roger
Department of Physiology, Trinity College, Dublin 2, Ireland.
J Neurophysiol. 2006 Jun;95(6):3519-27. doi: 10.1152/jn.01235.2005.
The induction of NMDA-receptor-dependent long-term potentiation (LTP) in adult CA1 is contingent on activation of Ca/calmodulin-dependent protein kinase II (CaMKII). However, little is known about kinase mediation of LTP in the dentate gyrus. In the present study, the involvement of the kinases CaMKII, PKA, and MAPK in the induction of LTP was studied in the dentate gyrus of adult rats. Individual application of selective inhibitors of CaMKII, MEK, or PKA did not inhibit induction of LTP. In contrast, coapplication of a CaMKII inhibitor with either a PKA or MEK inhibitor resulted in a strong block of LTP. Induction of LTP was blocked by the coapplication of the inhibitors CaMKII and PKA or MEK, both when they were applied 1 h before the induction stimulus and also when they were applied after the induction stimulus. Thus LTP is mediated by either of two parallel cascades, one involving CaMKII and the other PKA or MAPK. Moreover, these cascades are active for a certain period after the induction stimulus.
成年CA1区中N-甲基-D-天冬氨酸受体依赖的长时程增强（LTP）的诱导取决于钙/钙调蛋白依赖性蛋白激酶II（CaMKII）的激活。然而，关于齿状回中LTP的激酶介导作用却知之甚少。在本研究中，我们在成年大鼠的齿状回中研究了激酶CaMKII、蛋白激酶A（PKA）和丝裂原活化蛋白激酶（MAPK）在LTP诱导中的作用。单独应用CaMKII、MEK或PKA的选择性抑制剂并不会抑制LTP的诱导。相反，将CaMKII抑制剂与PKA或MEK抑制剂共同应用会导致LTP的强烈阻断。当在诱导刺激前1小时应用抑制剂CaMKII和PKA或MEK，以及在诱导刺激后应用时，LTP的诱导均被阻断。因此，LTP由两个平行级联中的任何一个介导，一个涉及CaMKII，另一个涉及PKA或MAPK。此外，这些级联在诱导刺激后的一段时间内是活跃的。
