神經(jīng)傳輸物質(zhì)在神經(jīng)末梢的釋放是由鈣離子的流入觸發(fā)的,,其流入是響應(yīng)于神經(jīng)脈沖進行的——可以是自然進行的, 也可以是作為動作電位進行的,。在后一種情況下,,釋放是快速的(和同步的)或延遲的(非同步的)。Jianyuan Sun等人利用遺傳學(xué)和電生理學(xué)工具,,將同步和非同步釋放區(qū)分了開來,,并且提出二者存在獨立的鈣傳感器。他們還建立了一個定量模型,,來解釋突觸傳輸?shù)拟}依賴性的所有情況,。
原始出處:
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: [email protected]) or T.C.S. (Email: [email protected]).
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.