Sakaba Takeshi, Neher Erwin
Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
Nature. 2003 Aug 14;424(6950):775-8. doi: 10.1038/nature01859.
Second messenger cascades involving G proteins and calcium are known to modulate neurotransmitter release. A prominent effect of such a cascade is the downmodulation of presynaptic calcium influx, which markedly reduces evoked neurotransmitter release. Here we show that G-protein-mediated signalling, such as through GABA (gamma-amino butyric acid) subtype B (GABA(B)) receptors, retards the recruitment of synaptic vesicles during sustained activity and after short-term depression. This retardation occurs through a lowering of cyclic AMP, which blocks the stimulatory effect of increased calcium concentration on vesicle recruitment. In this signalling pathway, cAMP (functioning through the cAMP-dependent guanine nucleotide exchange factor) and calcium/calmodulin cooperate to enhance vesicle priming. The differential modulation of the two forms of synaptic plasticity, presynaptic inhibition and calcium-dependent recovery from synaptic depression, is expected to have interesting consequences for the dynamic behaviour of neural networks.
已知涉及G蛋白和钙的第二信使级联反应可调节神经递质释放。这种级联反应的一个显著作用是下调突触前钙内流，这会显著减少诱发的神经递质释放。我们在此表明，G蛋白介导的信号传导，如通过γ-氨基丁酸B型（GABA(B)）受体，在持续活动期间和短期抑制后会延迟突触小泡的募集。这种延迟是通过降低环磷酸腺苷（cAMP）来实现的，它会阻断钙浓度升高对小泡募集的刺激作用。在这个信号通路中，cAMP（通过依赖cAMP的鸟嘌呤核苷酸交换因子发挥作用）和钙/钙调蛋白协同作用以增强小泡的启动。突触可塑性的两种形式，即突触前抑制和从突触抑制中钙依赖性恢复的差异调节，预计会对神经网络的动态行为产生有趣的影响。
