Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
J Gen Physiol
2001 Aug 01;1182:145-56. doi: 10.1085/jgp.118.2.145.
Show Gene links
Show Anatomy links
A kinetic analysis of calcium-triggered exocytosis.
Blank PS
,
Vogel SS
,
Malley JD
,
Zimmerberg J
.
???displayArticle.abstract???
Although the relationship between exocytosis and calcium is fundamental both to synaptic and nonneuronal secretory function, analysis is problematic because of the temporal and spatial properties of calcium, and the fact that vesicle transport, priming, retrieval, and recycling are coupled. By analyzing the kinetics of sea urchin eggsecretory vesicle exocytosis in vitro, the final steps of exocytosis are resolved. These steps are modeled as a three-state system: activated, committed, and fused, where interstate transitions are given by the probabilities that an active fusion complex commits (alpha) and that a committed fusion complex results in fusion, p. The number of committed complexes per vesicle docking site is Poisson distributed with mean n. Experimentally, p and n increase with increasing calcium, whereas alpha and the pn ratio remain constant, reducing the kinetic description to only one calcium-dependent, controlling variable, n. On average, the calcium dependence of the maximum rate (R(max)) and the time to reach R(max) (T(peak)) are described by the calcium dependence of n. Thus, the nonlinear relationship between the free calcium concentration and the rate of exocytosis can be explained solely by the calcium dependence of the distribution of fusion complexes at vesicle docking sites.
???displayArticle.pubmedLink???
11479342
???displayArticle.pmcLink???PMC2233829 ???displayArticle.link???J Gen Physiol ???displayArticle.grants???[+]
Figure 1. Typical fusion curves resulting from single and double challenge experiments at four different calcium concentrations are represented (14, 24, 35, and 76 μM). The data were collected using a sample time of 0.1 s The second fusion curve of a double challenge experiment was fit piecewise using a modification of the model. A fourth scaling parameter was used to represent the extent of fusion at the time of the second challenge. The data are black, the fitted curves are red, and the difference between the two (residuals) is green.
Figure 2. Dependence of p, n, α, and p
n on calcium concentration (mean ± SEM; A–D). Open symbols represent the fitting results of double challenge experiments using the same final calcium concentration, as indicated by the matching closed symbols, of single challenge experiments.
Figure 3. The maximum fusion rate and the time to reach the maximum rate (TPeak) vary with calcium. Using the relationship between the extent of fusion (pCa and n), the experimentally derived constants for α, and the correlation between n and p, specifies the kinetic response as a function of calcium. The solid lines indicate these relationships, in agreement with the observed behavior of both the maximum rate and the time to reach the maximum rate.
Figure 4. A and B represent the calcium-triggered response in two systems showing egglike and neuronlike kinetic behaviors with parameters n = 5, τα = 10 s, and τP = 7 s, and n = 0.2, τα = 10 ms, and τP = 7 ms, respectively. The rates were calculated using a total releasable pool of 1,000 vesicles. Note, the kinetics of the neuronlike system is ∼100× faster than that of the egglike system.
Figure 5. A and B are the log-log representations for the calcium dependence of the extent and maximum fusion rate predicted for the neuronlike system with τα = 10 ms and τP = 7 ms. The n-calcium relationship was established using midpoint M = 10 μM and width W = 0.23 in the cumulative log-normal distribution. The straight lines are nth order fits to the linear portions of the curve (3–7 μM calcium); the extent and maximum rate are approximated by [Ca2+]4.0 and [Ca2+]3.9, respectively. C is the predicted calcium dependence for the time of the first fusion event (Lag) and the time to reach the maximum rate (Tpeak).
Augustine,
Calcium entry and transmitter release at voltage-clamped nerve terminals of squid.
1985, Pubmed
Augustine,
Calcium entry and transmitter release at voltage-clamped nerve terminals of squid.
1985,
Pubmed
Augustine,
Calcium dependence of presynaptic calcium current and post-synaptic response at the squid giant synapse.
1986,
Pubmed
Augustine,
Calcium requirements for secretion in bovine chromaffin cells.
1992,
Pubmed
Avery,
In vitro exocytosis in sea urchin eggs requires a synaptobrevin-related protein.
1997,
Pubmed
,
Echinobase
Bertram,
Single-domain/bound calcium hypothesis of transmitter release and facilitation.
1996,
Pubmed
Bittner,
Kinetic analysis of secretion from permeabilized adrenal chromaffin cells reveals distinct components.
1992,
Pubmed
Blank,
Submaximal responses in calcium-triggered exocytosis are explained by differences in the calcium sensitivity of individual secretory vesicles.
1998,
Pubmed
,
Echinobase
Blank,
The calcium sensitivity of individual secretory vesicles is invariant with the rate of calcium delivery.
1998,
Pubmed
,
Echinobase
Bollmann,
Calcium sensitivity of glutamate release in a calyx-type terminal.
2000,
Pubmed
Borst,
Calcium influx and transmitter release in a fast CNS synapse.
1996,
Pubmed
Chad,
Calcium domains associated with individual channels can account for anomalous voltage relations of CA-dependent responses.
1984,
Pubmed
Charlton,
Role of presynaptic calcium ions and channels in synaptic facilitation and depression at the squid giant synapse.
1982,
Pubmed
Conner,
Members of the SNARE hypothesis are associated with cortical granule exocytosis in the sea urchin egg.
1997,
Pubmed
,
Echinobase
Coorssen,
Biochemical and functional studies of cortical vesicle fusion: the SNARE complex and Ca2+ sensitivity.
1998,
Pubmed
,
Echinobase
Diamond,
Asynchronous release of synaptic vesicles determines the time course of the AMPA receptor-mediated EPSC.
1995,
Pubmed
Dodge,
Co-operative action a calcium ions in transmitter release at the neuromuscular junction.
1967,
Pubmed
Gillis,
Protein kinase C enhances exocytosis from chromaffin cells by increasing the size of the readily releasable pool of secretory granules.
1996,
Pubmed
Heidelberger,
Calcium dependence of the rate of exocytosis in a synaptic terminal.
1994,
Pubmed
Heinemann,
Kinetics of the secretory response in bovine chromaffin cells following flash photolysis of caged Ca2+.
1994,
Pubmed
Heinemann,
A two-step model of secretion control in neuroendocrine cells.
1993,
Pubmed
Hide,
Degranulation of individual mast cells in response to Ca2+ and guanine nucleotides: an all-or-none event.
1993,
Pubmed
Huang,
Ca(2+)-dependent exocytosis in the somata of dorsal root ganglion neurons.
1996,
Pubmed
Kasai,
Two components of exocytosis and endocytosis in phaeochromocytoma cells studied using caged Ca2+ compounds.
1996,
Pubmed
Klingauf,
Modeling buffered Ca2+ diffusion near the membrane: implications for secretion in neuroendocrine cells.
1997,
Pubmed
Knight,
Gaining access to the cytosol: the technique and some applications of electropermeabilization.
1986,
Pubmed
Knight,
Exocytosis from the vesicle viewpoint: an overview.
1987,
Pubmed
Llinás,
Presynaptic calcium currents and their relation to synaptic transmission: voltage clamp study in squid giant synapse and theoretical model for the calcium gate.
1976,
Pubmed
Llinás,
Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse.
1981,
Pubmed
Murthy,
Heterogeneous release properties of visualized individual hippocampal synapses.
1997,
Pubmed
Murthy,
Reversal of synaptic vesicle docking at central synapses.
1999,
Pubmed
Neher,
Multiple calcium-dependent processes related to secretion in bovine chromaffin cells.
1993,
Pubmed
Nüsse,
Ca2+-induced exocytosis in individual human neutrophils: high- and low-affinity granule populations and submaximal responses.
1998,
Pubmed
Parsons,
Docked granules, the exocytic burst, and the need for ATP hydrolysis in endocrine cells.
1995,
Pubmed
Rosenmund,
Definition of the readily releasable pool of vesicles at hippocampal synapses.
1996,
Pubmed
Schneggenburger,
Intracellular calcium dependence of transmitter release rates at a fast central synapse.
2000,
Pubmed
Schneggenburger,
Released fraction and total size of a pool of immediately available transmitter quanta at a calyx synapse.
1999,
Pubmed
Schroeder,
Surface area change at fertilization: resorption of the mosaic membrane.
1979,
Pubmed
,
Echinobase
Simon,
Compartmentalization of the submembrane calcium activity during calcium influx and its significance in transmitter release.
1985,
Pubmed
Stevens,
Activity-dependent modulation of the rate at which synaptic vesicles become available to undergo exocytosis.
1998,
Pubmed
Tahara,
Calcium can disrupt the SNARE protein complex on sea urchin egg secretory vesicles without irreversibly blocking fusion.
1998,
Pubmed
,
Echinobase
Thomas,
A low affinity Ca2+ receptor controls the final steps in peptide secretion from pituitary melanotrophs.
1993,
Pubmed
Tse,
Local Ca2+ release from internal stores controls exocytosis in pituitary gonadotrophs.
1997,
Pubmed
Voets,
Mechanisms underlying phasic and sustained secretion in chromaffin cells from mouse adrenal slices.
1999,
Pubmed
Vogel,
Poisson-distributed active fusion complexes underlie the control of the rate and extent of exocytosis by calcium.
1996,
Pubmed
,
Echinobase
Wu,
The reduced release probability of releasable vesicles during recovery from short-term synaptic depression.
1999,
Pubmed
Yamada,
Time course of transmitter release calculated from simulations of a calcium diffusion model.
1992,
Pubmed
Zimmerberg,
A stage-specific preparation to study the Ca(2+)-triggered fusion steps of exocytosis: rationale and perspectives.
2000,
Pubmed
,
Echinobase
Zimmerberg,
Exocytosis of sea urchin egg cortical vesicles in vitro is retarded by hyperosmotic sucrose: kinetics of fusion monitored by quantitative light-scattering microscopy.
1985,
Pubmed
,
Echinobase
Zimmerberg,
Sea urchin egg preparations as systems for the study of calcium-triggered exocytosis.
1999,
Pubmed
,
Echinobase
Zucker,
Relationship between transmitter release and presynaptic calcium influx when calcium enters through discrete channels.
1986,
Pubmed
Zucker,
Presynaptic calcium in transmitter release and posttetanic potentiation.
1991,
Pubmed
Zucker,
Exocytosis: a molecular and physiological perspective.
1996,
Pubmed
von Gersdorff,
Dynamics of synaptic vesicle fusion and membrane retrieval in synaptic terminals.
1994,
Pubmed
von Rüden,
A Ca-dependent early step in the release of catecholamines from adrenal chromaffin cells.
1993,
Pubmed
