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标题：Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling
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作者：Igor Delvendahl ; Lukasz Jablonski ; Carolin Baade 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：23
页码：E3075-E3084
DOI：10.1073/pnas.1508419112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceCalcium influx during action potentials triggers neurotransmitter release at presynaptic active zones. Calcium buffers limit the spread of calcium and restrict neurotransmitter release to the vicinity of calcium channels. To sustain synchronous release during repetitive activity, rapid removal of calcium from the active zone is essential, but the underlying mechanisms are unclear. Therefore, we focused on cerebellar mossy fiber synapses, which are among the fastest synapses in the mammalian brain and found very weak presynaptic calcium buffering. One might assume that strong calcium buffering has the potential to efficiently remove calcium from active zones. In contrast, our results show that weak calcium buffering speeds active zone calcium clearance. Thus, the strength of presynaptic buffering limits the rate of synaptic transmission. Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca2+ signals, which are confined in their spatiotemporal extent by endogenous Ca2+ buffers. However, it remains elusive how rapid and reliable Ca2+ signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca2+ imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca2+-binding ratio ([~]15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca2+ from the active zone during repetitive firing. Measuring Ca2+ signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca2+ buffering enables fast active zone Ca2+ signaling, suggesting that the strength of endogenous Ca2+ buffering limits the rate of synchronous synaptic transmission.
关键词：active zone ; calcium signaling ; presynaptic ; neurotransmitter release ; calcium buffers