Schwartz Eric J, Blackmer Trillium, Gerachshenko Tatyana, Alford Simon
Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
J Neurosci. 2007 May 30;27(22):5857-68. doi: 10.1523/JNEUROSCI.1160-07.2007.
When synaptic vesicles fuse with the plasma membrane, they may completely collapse or fuse transiently. Transiently fusing vesicles remain structurally intact and therefore have been proposed to represent a form of rapid vesicle recycling. However, the impact of a transient synaptic vesicle fusion event on neurotransmitter release, and therefore on synaptic transmission, has yet to be determined. Recently, the molecular mechanism by which a serotonergic presynaptic G-protein-coupled receptor (GPCR) regulates synaptic vesicle fusion and inhibits synaptic transmission was identified. By making paired electrophysiological recordings in the presence and absence of low-affinity antagonists, we now demonstrate that activation of this presynaptic GPCR lowers the peak synaptic cleft glutamate concentration independently of the probability of vesicle fusion. Furthermore, this change in cleft glutamate concentration differentially inhibits synaptic NMDA and AMPA receptor-mediated currents. We conclude that a presynaptic GPCR regulates the profile of glutamate in the synaptic cleft through altering the mechanism of vesicle fusion leading to qualitative as well as quantitative changes in neural signaling.
当突触小泡与质膜融合时，它们可能会完全塌陷或短暂融合。短暂融合的小泡在结构上保持完整，因此有人提出这代表了一种快速的小泡循环形式。然而，短暂的突触小泡融合事件对神经递质释放以及突触传递的影响尚未确定。最近，一种血清素能突触前G蛋白偶联受体（GPCR）调节突触小泡融合并抑制突触传递的分子机制被确定。通过在存在和不存在低亲和力拮抗剂的情况下进行配对电生理记录，我们现在证明，这种突触前GPCR的激活独立于小泡融合的概率降低了突触间隙谷氨酸的峰值浓度。此外，突触间隙谷氨酸浓度的这种变化差异性地抑制了突触NMDA和AMPA受体介导的电流。我们得出结论，突触前GPCR通过改变小泡融合机制来调节突触间隙中谷氨酸的分布，从而导致神经信号在质量和数量上的变化。
