From calcium blips to calcium puffs: Theoretical analysis of the requirements for interchannel communication

Swillens, Stéphane; Dupont, Geneviève; Combettes, Laurent; Champeil, Philippe

doi:10.1073/pnas.96.24.13750

Cited by 163 publications

(199 citation statements)

References 30 publications

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“…The number of receptors in a cluster has not been measured yet. We employ N = 25 following recent estimates by Swillens and Dupont [7]. The probability distributions p(n 3 + n 4 ) with h = 4 and p(n 3 ) with h = 3 are depicted in figure 8.…”

Section: Discussionmentioning

confidence: 99%

“…This region is usually not connected. However, Swillens et al showed that the spatial arrangement of IP 3 R channels does not influence the Ca 2+ dynamics at an open cluster [7]. Therefore, we map the area of all conducting release channels to an area of the same size concentric to the cluster area.…”

Section: Ca 2+ Modelmentioning

confidence: 99%

“…Release is controlled by inositol-1,4,5-trisphosphate (IP 3 ) receptor channels (IP 3 R). They are arranged in clusters that comprise between 1 and 40 channels and that are randomly distributed on the membrane of the ER with distances between 1-7 µm [7,8]. IP 3 Rs have the important property that their open probability depends on the Ca 2+ concentration in the cytosol.…”

Section: Introductionmentioning

confidence: 99%

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Frequency of elemental events of intracellularCa2+dynamics

Thul¹,

Falcke²

2006

Phys. Rev. E

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The dynamics of intracellular Ca 2+ is driven by random events called Ca 2+ puffs, in which Ca 2+ is liberated from intracellular stores. We show that the emergence of Ca 2+ puffs can be mapped to an escape process. The mean first passage times that correspond to the stochastic fraction of puff periods are computed from a novel master equation and two Fokker-Planck equations. Our results demonstrate that the mathematical modeling of Ca 2+ puffs has to account for the discrete character of the Ca 2+ release sites and does not permit a continuous description of the number of open channels.

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Section: Discussionmentioning

confidence: 99%

Section: Ca 2+ Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Frequency of elemental events of intracellularCa2+dynamics

Thul¹,

Falcke²

2006

Phys. Rev. E

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“…This small size of a cluster allows us to assume that the Ca 2ϩ is constant within the cluster (see also ref. 17). This in turn allows us to model the Ca 2ϩ flux from the ER into the cytosol as a point source with a weight factor that describes the strengths (size) of the source.…”

Section: Model For Intracellular Ca 2؉ Responsementioning

confidence: 99%

“…They are involved, e.g., in the stimulus-induced contraction in smooth muscle cells (11), in the hormone-induced glucose production in liver cells (12), and for the early response to injury of brain tissue (13) and corneal epithelia (14). Recent new insights into the biophysical mechanism of intracellular Ca 2ϩ release have revealed that the actual release sites are discrete and as small as Ϸ100-200 nm comprising only 20-50 release channels (15)(16)(17). The clustering of these channels is well documented in various cell types and may be a universal feature of the Ca 2ϩ release mechanism.…”

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confidence: 99%

Optimal ion channel clustering for intracellular calcium signaling

Shuai

Jung

2003

Proc. Natl. Acad. Sci. U.S.A.

176

102

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Ion channels and receptors in the cell membranes and internal membranes are often distributed in discrete clusters. One particularly well-studied example is the distribution of inositol 1,4,5-triphosphate receptors in the plasma membrane that controls the flux of Ca 2؉ from the endoplasmic reticulum into the cytosol. By using mathematical modeling, we show that channel clustering can enhance the cell's Ca 2؉ signaling capability. Furthermore, we predict optimal signaling cellular capability at cluster sizes and distances that agree with experimentally found values in Xenopus oocyte.channel dynamics ͉ Markov process ͉ noise R eceptors and ion channels play an important role in cellular homeostasis. They regulate electric membrane potentials and cell volume and turn on and off signaling cascades within the cell. Highly resolved fluorescent imaging and antibody labeling technology have revealed that the channel and receptor proteins are frequently not uniformly distributed over the membrane but rather form small clusters sometimes only on the nanometer scale (for a review see ref. 1). One possible mechanism that leads to clustering is based on the formation of microdomains of the lipid bilayer of the membrane. These microdomains, the socalled rafts (2), are more likely to bind specific proteins and form a, possibly moving, platform for protein trafficking, or signal relay stations for intracellular signaling. Other proposed mechanisms for clustering involve the cytoskeleton (3). Here, microtubules in the membrane undercoat anchor channels that otherwise would perform free motion through the cell membrane. As a result, m 2 -sized clusters of ion channels form on the axon of e.g., rat retinal ganglion cell. In recent work by Clay and Kuzirian (4-6) it has been discovered that potassium channels in the squid giant axon are clustered. Evidence has been presented that vesicles containing potassium channels are contacting the cluster sites and facilitate channel turnover.Clustering of chemotactic receptors on Escherichia coli has been shown to constrain sensitivity of signaling in response to receptor binding (7). Binding of the chemotactic receptor inactivates a downstream intracellular signaling pathway. If there is cooperativity between neighboring receptors, in the sense that an activated receptor in turn activates receptors in its neighborhood, it is clear that this cooperativity will enhance the response by increasing the change in number of activated receptors. If the numbers of receptors is limited, however, increasing spatial range of cooperation between the receptors (i.e., cluster sizes) increases the response to a small number of binding agonist but does not leave room for differential response to stimuli of different intensity. It has been proposed that distributions of receptors in clusters of variable sizes optimize the response to small stimuli and the sensitivity to signal amplitudes (7).We propose a different role for the clustering of receptors and ion channels in the membrane. We do not attempt to ans...

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Biological Rhythms as Temporal Dissipative Structures

Goldbeter

2007

Advances in Chemical Physics

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From calcium blips to calcium puffs: Theoretical analysis of the requirements for interchannel communication

Cited by 163 publications

References 30 publications

Frequency of elemental events of intracellularCa2+dynamics

Frequency of elemental events of intracellularCa2+dynamics

Optimal ion channel clustering for intracellular calcium signaling

Biological Rhythms as Temporal Dissipative Structures

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