Wang J H, Kelly P T
Department of Neurobiology and Anatomy, University of Texas, Houston 77225, USA.
Neuron. 1995 Aug;15(2):443-52. doi: 10.1016/0896-6273(95)90048-9.
CA2+-regulated protein kinases play critical roles in long-term potentiation (LTP). To understand the role of Ca2+/calmodulin (CaM) signaling pathways in synaptic transmission better, Ca2+/CaM was injected into hippocampal CA1 neurons. Ca2+/CaM induced significant potentiation of excitatory synaptic responses, which was blocked by coinjection of a CaM-binding peptide and was not induced by injections of Ca2+ or CaM alone. Reciprocal experiments demonstrated that Ca2+/CaM-induced synaptic potentiation and tetanus-induced LTP occluded one another. Pseudosubstrate inhibitors or high-affinity substrates of CaMKII or PKC blocked Ca2/CaM-induced potentiation, indicating the requirement of CaMKII and PKC activities in synaptic potentiation. We suggest that postsynaptic levels of free Ca2+/CaM is a rate limiting factor and that functional cross-talk between Ca2+/CaM and PKC pathways occurs during the induction of LTP.
钙离子调节的蛋白激酶在长时程增强（LTP）中发挥关键作用。为了更好地理解Ca2+/钙调蛋白（CaM）信号通路在突触传递中的作用，将Ca2+/CaM注入海马CA1神经元。Ca2+/CaM诱导兴奋性突触反应显著增强，这种增强被共注射CaM结合肽所阻断，单独注射Ca2+或CaM则不会诱导这种增强。反向实验表明，Ca2+/CaM诱导的突触增强和强直刺激诱导的LTP相互抵消。CaMKII或PKC的假底物抑制剂或高亲和力底物阻断了Ca2/CaM诱导的增强，表明CaMKII和PKC活性在突触增强中是必需的。我们认为突触后游离Ca2+/CaM水平是一个限速因素，并且在LTP诱导过程中Ca2+/CaM与PKC通路之间发生功能性相互作用。
