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

Article

关键词: SHORT-TERM DEPRESSION;    CALCIUM-CHANNEL TYPES;    TRANSMITTER RELEASE;    SYNAPTOTAGMIN-I;    ASYNCHRONOUS RELEASE;    DETERMINES FAST;    CA2+ CHANNELS;    CALYX;    MODULATION;    SENSOR;   

DOI  :  10.1038/nature06308

来源: SCIE

【 摘 要 】

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 similar to 2 with a Ca2+ affinity of similar to 44 mu M, in contrast to synchronous release, which exhibits a Ca2+ cooperativity of similar to 5 with a Ca2+ affinity of similar to 38 mu M. 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.

【 授权许可】

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