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Publication : A dual-Ca2+-sensor model for neurotransmitter release in a central synapse.

First Author  Sun J Year  2007
Journal  Nature Volume  450
Issue  7170 Pages  676-82
PubMed ID  18046404 Mgi Jnum  J:130379
Mgi Id  MGI:3771537 Doi  10.1038/nature06308
Citation  Sun J, et al. (2007) A dual-Ca2+-sensor model for neurotransmitter release in a central synapse. Nature 450(7170):676-82
abstractText  Ca2+-triggered synchronous neurotransmitter release is well described, but asynchronous release-in fact, its very existence-remains enigmatic. Here we report a quantitative description of asynchronous neurotransmitter release in calyx-of-Held synapses. We show that deletion of synaptotagmin 2 (Syt2) in mice selectively abolishes synchronous release, allowing us to study pure asynchronous release in isolation. Using photolysis experiments of caged Ca2+, we demonstrate that asynchronous release displays a Ca2+ cooperativity of approximately 2 with a Ca2+ affinity of approximately 44 microM, in contrast to synchronous release, which exhibits a Ca2+ cooperativity of approximately 5 with a Ca2+ affinity of approximately 38 muM. Our results reveal that release triggered in wild-type synapses at low Ca2+ concentrations is physiologically asynchronous, and that asynchronous release completely empties the readily releasable pool of vesicles during sustained elevations of Ca2+. We propose a dual-Ca2+-sensor model of release that quantitatively describes the contributions of synchronous and asynchronous release under conditions of different presynaptic Ca2+ dynamics.
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