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. |