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Modulation of elementary calcium release mediates a transition from puffs to waves in an IP3R cluster model.

Rückl M, Parker I, Marchant JS, Nagaiah C, Johenning FW, Rüdiger S - PLoS Comput. Biol. (2015)

Bottom Line: For increasing IP3 concentration, the release events become modulated at a timescale of minutes, with repetitive wave-like releases interspersed with several puffs.This modulation is consistent with experimental observations we present, including refractoriness and increase of puff frequency during the inter-wave interval.Our results suggest that waves are established by a random but time-modulated appearance of sustained release events, which have a high potential to trigger and synchronize activity throughout the cell.

View Article: PubMed Central - PubMed

Affiliation: Institut für Physik, Humboldt-Universität zu Berlin, Berlin, Germany.

ABSTRACT
The oscillating concentration of intracellular calcium is one of the most important examples for collective dynamics in cell biology. Localized releases of calcium through clusters of inositol 1,4,5-trisphosphate receptor channels constitute elementary signals called calcium puffs. Coupling by diffusing calcium leads to global releases and waves, but the exact mechanism of inter-cluster coupling and triggering of waves is unknown. To elucidate the relation of puffs and waves, we here model a cluster of IP3R channels using a gating scheme with variable non-equilibrium IP3 binding. Hybrid stochastic and deterministic simulations show that puffs are not stereotyped events of constant duration but are sensitive to stimulation strength and residual calcium. For increasing IP3 concentration, the release events become modulated at a timescale of minutes, with repetitive wave-like releases interspersed with several puffs. This modulation is consistent with experimental observations we present, including refractoriness and increase of puff frequency during the inter-wave interval. Our results suggest that waves are established by a random but time-modulated appearance of sustained release events, which have a high potential to trigger and synchronize activity throughout the cell.

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(A) Event duration depends on the number of activatable channels at the beginning of an event. While low numbers of activatable channels very likely will lead to short events, large numbers do not necessarily lead to long events. (B) The number of activatable channels at the end of an event as a function of the duration. Bars denote standard deviations. Absent bars indicate single observations.
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pcbi-1003965-g005: (A) Event duration depends on the number of activatable channels at the beginning of an event. While low numbers of activatable channels very likely will lead to short events, large numbers do not necessarily lead to long events. (B) The number of activatable channels at the end of an event as a function of the duration. Bars denote standard deviations. Absent bars indicate single observations.

Mentions: Fig. 5 A shows that there is indeed a strong correlation between the number of activatable channels and the event duration. Events starting with only a low number (below 4 or 5) of activatable channels reliably terminate fast. For an intermediate number of activatable channels (6 to 9), there still is a strong stochastic variability of event durations. Finally, for a sufficiently high number almost all events last longer than a few seconds. In other words: a high number of activatable channels is necessary to produce a long event. In the intermediate regime (6 to 9 activatable channels), the time course of the events furthermore depends on the details of the channels' states, e.g. whether activatable channels have 3 or 4 subunits with bound IP3 (data not shown).


Modulation of elementary calcium release mediates a transition from puffs to waves in an IP3R cluster model.

Rückl M, Parker I, Marchant JS, Nagaiah C, Johenning FW, Rüdiger S - PLoS Comput. Biol. (2015)

(A) Event duration depends on the number of activatable channels at the beginning of an event. While low numbers of activatable channels very likely will lead to short events, large numbers do not necessarily lead to long events. (B) The number of activatable channels at the end of an event as a function of the duration. Bars denote standard deviations. Absent bars indicate single observations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288706&req=5

pcbi-1003965-g005: (A) Event duration depends on the number of activatable channels at the beginning of an event. While low numbers of activatable channels very likely will lead to short events, large numbers do not necessarily lead to long events. (B) The number of activatable channels at the end of an event as a function of the duration. Bars denote standard deviations. Absent bars indicate single observations.
Mentions: Fig. 5 A shows that there is indeed a strong correlation between the number of activatable channels and the event duration. Events starting with only a low number (below 4 or 5) of activatable channels reliably terminate fast. For an intermediate number of activatable channels (6 to 9), there still is a strong stochastic variability of event durations. Finally, for a sufficiently high number almost all events last longer than a few seconds. In other words: a high number of activatable channels is necessary to produce a long event. In the intermediate regime (6 to 9 activatable channels), the time course of the events furthermore depends on the details of the channels' states, e.g. whether activatable channels have 3 or 4 subunits with bound IP3 (data not shown).

Bottom Line: For increasing IP3 concentration, the release events become modulated at a timescale of minutes, with repetitive wave-like releases interspersed with several puffs.This modulation is consistent with experimental observations we present, including refractoriness and increase of puff frequency during the inter-wave interval.Our results suggest that waves are established by a random but time-modulated appearance of sustained release events, which have a high potential to trigger and synchronize activity throughout the cell.

View Article: PubMed Central - PubMed

Affiliation: Institut für Physik, Humboldt-Universität zu Berlin, Berlin, Germany.

ABSTRACT
The oscillating concentration of intracellular calcium is one of the most important examples for collective dynamics in cell biology. Localized releases of calcium through clusters of inositol 1,4,5-trisphosphate receptor channels constitute elementary signals called calcium puffs. Coupling by diffusing calcium leads to global releases and waves, but the exact mechanism of inter-cluster coupling and triggering of waves is unknown. To elucidate the relation of puffs and waves, we here model a cluster of IP3R channels using a gating scheme with variable non-equilibrium IP3 binding. Hybrid stochastic and deterministic simulations show that puffs are not stereotyped events of constant duration but are sensitive to stimulation strength and residual calcium. For increasing IP3 concentration, the release events become modulated at a timescale of minutes, with repetitive wave-like releases interspersed with several puffs. This modulation is consistent with experimental observations we present, including refractoriness and increase of puff frequency during the inter-wave interval. Our results suggest that waves are established by a random but time-modulated appearance of sustained release events, which have a high potential to trigger and synchronize activity throughout the cell.

Show MeSH