神经传输物质在神经末梢的释放是由钙离子的流入触发的,其流入是响应于神经脉冲进行的——可以是自然进行的, 也可以是作为动作电位进行的。在后一种情况下,释放是快速的(和同步的)或延迟的(非同步的)。Jianyuan Sun等人利用遗传学和电生理学工具,将同步和非同步释放区分了开来,并且提出二者存在独立的钙传感器。他们还建立了一个定量模型,来解释突触传输的钙依赖性的所有情况。
原始出处:
Nature 450, 676-682 (29 November 2007) | doi:10.1038/nature06308; Received 20 August 2007; Accepted 24 September 2007
A dual-Ca2+-sensor model for neurotransmitter release in a central synapse
Jianyuan Sun1,2, Zhiping P. Pang1, Dengkui Qin1, Abigail T. Fahim4, Roberto Adachi4 & Thomas C. Südhof1,2,3
Departments of Neuroscience and,
Molecular Genetics, and,
Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Department of Pulmonary Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
Correspondence to: Jianyuan Sun1,2Thomas C. Südhof1,2,3 Correspondence and requests for materials should be addressed to J.S. (Email: Jianyuan.Sun@UTSouthwestern.edu) or T.C.S. (Email: Thomas.Sudhof@UTSouthwestern.edu).
Abstract
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 2 with a Ca2+ affinity of 44 M, in contrast to synchronous release, which exhibits a Ca2+ cooperativity of 5 with a Ca2+ affinity of 38 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.