CALCIUM CALMODULIN-DEPENDENT KINASE-II AND LONG-TERM POTENTIATION ENHANCE SYNAPTIC TRANSMISSION BY THE SAME MECHANISM
CALCIUM CALMODULIN-DEPENDENT KINASE-II AND LONG-TERM POTENTIATION ENHANCE SYNAPTIC TRANSMISSION BY THE SAME MECHANISM
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DOI：
10.1073/pnas.92.24.11175
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发表时间：
1995-11-21
影响因子：
11.1
通讯作者：
NICOLL, RA
中科院分区：
文献类型：
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作者：
LLEDO, PM;HJELMSTAD, GO;NICOLL, RA
Ca2+ 敏感激酶被认为在长时程增强 (LTP) 中发挥作用，为了测试 Ca2+/钙调蛋白依赖性激酶 II (CaM-K II) 的参与，将该激酶的截短、组成型活性形式直接注射到 CA1 海马锥体细胞中。将 CaM-K II 纳入记录移液管会导致兴奋性突触后电流 (EPSC) 的大小逐渐增加。当移液管含有热失活激酶时，诱发反应没有发生变化。CaM-K II 的作用模仿了 LTP 的几个特征，即它导致突触衰竭的发生率降低、自发 EPSC 的大小增加以及对离子电渗疗法应用的 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸盐的反应幅度增加。为了确定 CaM-K II 诱导的增强和 LTP 是否具有共同的机制，进行了闭塞实验。 CaM-K II 的增强作用因 LTP 的预先诱导而大大减弱。此外，随着 CaM-K II 突触强度的增加，强直刺激无法诱发 LTP。这些发现表明，单独的 CaM-K II 就足以增强突触强度，并且这种增强与 LTP 观察到的增强具有相同的潜在机制。
Ca2+-sensitive kinases are thought to play a role in long-term potentiation (LTP), To test the involvement of Ca2+/calmodulin-dependent kinase II (CaM-K II), a truncated, constitutively active form of this kinase was directly injected into CA1 hippocampal pyramidal cells. Inclusion of CaM-K II in the recording pipette resulted in a gradual increase in the size of excitatory postsynaptic currents (EPSCs). No change in evoked responses occurred when the pipette contained heat-inactivated kinase, The effects of CaM-K II mimicked several features of LTP in that it caused a decreased incidence of synaptic failures, an increase in the size of spontaneous EPSCs, and an increase in the amplitude of responses to iontophoretically applied alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. To determine whether the CaM-K II-induced enhancement and LTP share a common mechanism, occlusion experiments were carried out. The enhancing action of CaM-K II was greatly diminished by prior induction of LTP. In addition, following the increase in synaptic strength by CaM-K II, tetanic stimulation failed to evoke LTP. These findings indicate that CaM-K II alone is sufficient to augment synaptic strength and that this enhancement shares the same underlying mechanism as the enhancement observed with LTP.`