Abstract:
:Calcium-triggered fusion of synaptic vesicles and neurotransmitter release are fundamental signalling steps in the central nervous system. It is generally assumed that fast transmitter release is triggered by elevations in intracellular calcium concentration ([Ca2+]i) to at least 100 microM near the sites of vesicle fusion. For synapses in the central nervous system, however, there are no experimental estimates of this local [Ca2+]i signal. Here we show, by using calcium ion uncaging in the large synaptic terminals of the calyx of Held, that step-like elevations to only 10 microM [Ca2+]i induce fast transmitter release, which depletes around 80% of a pool of available vesicles in less than 3 ms. Kinetic analysis of transmitter release rates after [Ca2+]i steps revealed the rate constants for calcium binding and vesicle fusion. These show that transient (around 0.5 ms) local elevations of [Ca2+]i to peak values as low as 25 microM can account for transmitter release during single presynaptic action potentials. The calcium sensors for vesicle fusion are far from saturation at normal release probability. This non-saturation, and the high intracellular calcium cooperativity in triggering vesicle fusion, make fast synaptic transmission very sensitive to modulation by changes in local [Ca2+]i.
journal_name
Naturejournal_title
Natureauthors
Schneggenburger R,Neher Edoi
10.1038/35022702keywords:
subject
Has Abstractpub_date
2000-08-24 00:00:00pages
889-93issue
6798eissn
0028-0836issn
1476-4687journal_volume
406pub_type
杂志文章相关文献
NATURE文献大全abstract::Osteoclasts are the only somatic cells with bone-resorbing capacity and, as such, they have a critical role not only in normal bone homeostasis (called 'bone remodelling') but also in the pathogenesis of bone destructive disorders such as rheumatoid arthritis and osteoporosis. A major focus of research in the field ha...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07713
更新日期:2009-03-26 00:00:00
abstract::The ability to generate patient-specific human induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling human disease and for individualizing drug testing. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death....
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09747
更新日期:2011-03-10 00:00:00
abstract::Self-incompatibility in flowering plants is often controlled by a single nuclear gene (the S-gene) having several alleles. This gene prevents fertilization by self-pollen or by pollen bearing either of the two S-alleles expressed in the style. Sequence analysis shows that three alleles of the S gene of Nicotiana alata...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/342955a0
更新日期:1989-12-21 00:00:00
abstract::Magma intrusions and eruptions commonly produce abrupt changes in seismicity far from magma conduits that cannot be associated with the diffusion of pore fluids or heat. Such 'swarm' seismicity also migrates with time, and often exhibits a 'dog-bone'-shaped distribution. The largest earthquakes in swarms produce after...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature00997
更新日期:2002-09-05 00:00:00
abstract::Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples fro...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04226
更新日期:2005-10-27 00:00:00
abstract::Long-term potentiation (LTP) and long-term depression (LTD) are activity-dependent changes in synaptic strength that may serve as the cellular mechanisms of information storage in the vertebrate brain. The mossy fibre-CA3 synapse displays NMDA (M-methyl-D-aspartate) receptor-independent forms of LTP and LTD that were ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/381429a0
更新日期:1996-05-30 00:00:00
abstract::Increased levels of brain amyloid-beta, a secreted peptide cleavage product of amyloid precursor protein (APP), is believed to be critical in the aetiology of Alzheimer's disease. Increased amyloid-beta can cause synaptic depression, reduce the number of spine protrusions (that is, sites of synaptic contacts) and bloc...
journal_title:Nature
pub_type: 评论,杂志文章
doi:10.1038/nature09217
更新日期:2010-08-12 00:00:00
abstract::The mushroom bodies in the protocerebrum are believed to be the structures of the insect brain most closely associated with higher-order sensory integration and learning. Drosophila melanogaster mutants with olfactory learning deficits have anatomically abnormal mushroom bodies or altered patterns of gene expression i...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/364238a0
更新日期:1993-07-15 00:00:00
abstract::Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal diffe...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11661
更新日期:2013-01-10 00:00:00
abstract::Double-stranded RNAs (dsRNAs) induce post-transcriptional gene silencing in several species of animal and plant. In plants, dsRNAs targeted to CpG islands within a promoter can also induce RNA-directed DNA methylation; however, it remains unclear whether gene silencing mediated by DNA methylation can be induced by dsR...
journal_title:Nature
pub_type: 杂志文章,收录出版
doi:10.1038/nature02889
更新日期:2004-09-09 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07324-x
更新日期:2018-11-01 00:00:00
abstract::Jupiter's ring system has previously been described as being composed of a 'bright' narrow ring and an interior, vertically-extended halo. The one image which reveals this morphology most clearly is Voyager 2's parting shot of the Jupiter system, a wide-angle (WA) view of the ring ansa in forward-scattered light (FDS...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/316526a0
更新日期:1985-08-08 00:00:00
abstract::We have previously identified a structurally abnormal insulin in the serum and pancreas of a middle-aged man with diabetes mellitus which arose from a leucine for phenylalanine substitution at position 24 or 25 of the insulin B chain; further analysis of the patient's leukocyte DNA showed that one of the patient's ins...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/302540a0
更新日期:1983-04-07 00:00:00
abstract::Osteoarthritis-the most common form of age-related degenerative whole-joint disease1-is primarily characterized by cartilage destruction, as well as by synovial inflammation, osteophyte formation and subchondral bone remodelling2,3. However, the molecular mechanisms that underlie the pathogenesis of osteoarthritis are...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-0920-1
更新日期:2019-02-01 00:00:00
abstract::Large-scale systematic sequencing has generally depended on the availability of an ordered library of large-insert bacterial or viral genomic clones for the organism under study. The generation of these large insert libraries, and the location of each clone on a genome map, is a laborious and time-consuming process. I...
journal_title:Nature
pub_type: 杂志文章
doi:
更新日期:1997-05-29 00:00:00
abstract::One reason for the failure of chemotherapy in the treatment of advanced cancers may be the outgrowth of multidrug-resistant tumour cells. Multidrug resistance has been modelled in numerous mammalian cell lines in which the phenotype is characterized by a pleiotropic cross-resistance to unrelated drugs. In the study re...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/316820a0
更新日期:1985-08-29 00:00:00
abstract::Greek speakers say "omicronupsilonrho", Germans "schwanz" and the French "queue" to describe what English speakers call a 'tail', but all of these languages use a related form of 'two' to describe the number after one. Among more than 100 Indo-European languages and dialects, the words for some meanings (such as 'tail...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06176
更新日期:2007-10-11 00:00:00
abstract::A newly-constructed antibody-like molecule containing the gp120-binding domain of the receptor for human immunodeficiency virus blocks HIV-1 infection of T cells and monocytes. Its long plasma half-life, other antibody-like properties, and potential to block all HIV isolates, make it a good candidate for therapeutic u...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/337525a0
更新日期:1989-02-09 00:00:00
abstract::Little is known about virus-host cell interactions that regulate the lytic potential of viruses during productive replication. Sindbis virus (SV), a single-stranded positive-sense RNA virus in the alphavirus genus (family Togaviridae), results in lytic infection in most vertebrate cell lines, but persistent productive...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/361739a0
更新日期:1993-02-25 00:00:00
abstract::In the absence of extraneously added template, standard preparations of Q beta replicase spontaneously synthesize RNA in vitro, possibly as a result of RNA contamination. Using special enzyme purifications, Sumper and Luce presented evidence that self-replicating RNA not present ab initio can grow out of 'template-fre...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/321089a0
更新日期:1986-05-01 00:00:00
abstract::The 20S cyclosome complex (also known as the anaphase-promoting complex) has ubiquitin ligase activity and is required for mitotic cyclin destruction and sister chromatid separation. The formation and activation of the 20S cyclosome complex is regulated by an unknown mechanism. Here we show that Cut4 (ref. 6) is an es...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/384276a0
更新日期:1996-11-21 00:00:00
abstract::Cells subjected to a heat shock, or a variety of other stresses increase the synthesis of a set of proteins, known as heat shock proteins. This response is apparently universal, occurring in the entire range from bacterial to mammalian cells. In Escherichia coli heat shock protein synthesis transiently increases follo...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/329348a0
更新日期:1987-09-24 00:00:00
abstract::Mammalian circadian clocks consist of complex integrated feedback loops that cannot be elucidated without comprehensive measurement of system dynamics and determination of network structures. To dissect such a complicated system, we took a systems-biological approach based on genomic, molecular and cell biological tec...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature00906
更新日期:2002-08-01 00:00:00
abstract::The human T cell erythrocyte receptor (CD2 antigen) allows thymocytes and mature T cells to adhere to thymic epithelium and target cells through a cell surface protein, LFA-3 (refs 1-6). Monoclonal antibodies recognizing CD2 can either block adhesion or, in certain combinations, induce an antigen-independent T cell ac...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/329842a0
更新日期:1987-10-29 00:00:00
abstract::Totipotent germline blastomeres in Caenorhabditis elegans contain, but do not respond to, factors that promote somatic differentiation in other embryonic cells. Mutations in the maternal gene pie-1 result in the germline blastomeres adopting somatic cell fates. Here we show that pie-1 encodes a nuclear protein, PIE-1,...
journal_title:Nature
pub_type: 信件
doi:10.1038/382710a0
更新日期:1996-08-22 00:00:00
abstract::Monocular lid suture during the sensitive period early in the life of a kitten disrupts normal development of inputs from the two eyes to the visual cortex, causing a decrease in the fraction of cortical cells responding to the deprived eye. Such an ocular dominance shift has been assumed to depend on patterned visual...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/324154a0
更新日期:1986-11-13 00:00:00
abstract::Statistical dependencies in the responses of sensory neurons govern both the amount of stimulus information conveyed and the means by which downstream neurons can extract it. Although a variety of measurements indicate the existence of such dependencies, their origin and importance for neural coding are poorly underst...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07140
更新日期:2008-08-21 00:00:00
abstract::Haematopoietic stem cells (HSCs) have the ability to renew themselves and to give rise to all lineages of the blood; however, the signals that regulate HSC self-renewal remain unclear. Here we show that the Wnt signalling pathway has an important role in this process. Overexpression of activated beta-catenin expands t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01593
更新日期:2003-05-22 00:00:00
abstract::Activity-induced changes in the efficacy of synaptic transmission between neurones are central to several prominent theories of learning. In both in vivo and in vitro preparations of the hippocampus, a conditioning high-frequency stimulus delivered to afferent fibres results in a long-term potentiation of synaptic tra...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/320529a0
更新日期:1986-04-10 00:00:00
abstract::The ATP-dependent chromatin assembly and remodelling factor (ACF) functions to generate regularly spaced nucleosomes, which are required for heritable gene silencing. The mechanism by which ACF mobilizes nucleosomes remains poorly understood. Here we report a single-molecule FRET study that monitors the remodelling of...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08627
更新日期:2009-12-24 00:00:00