Limits...
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.

Show MeSH
Distribution of event durations for [IP3] of 10 nM (red bars), 35 nM (green bars) and 70 nM (blue bars).For [IP3] = 10 nM only 3 of 90 events lasted longer than 2 s (3.3%). For [IP3] = 20 nM only 10 of 166 events lasted longer than 3 s (6.0%). For [IP3] = 80 nM, 72 of 309 events lasted longer than 3 s (23%). Error bars denote the sampling error of the histogram. The inset shows the average event duration and its standard deviation.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4288706&req=5

pcbi-1003965-g003: Distribution of event durations for [IP3] of 10 nM (red bars), 35 nM (green bars) and 70 nM (blue bars).For [IP3] = 10 nM only 3 of 90 events lasted longer than 2 s (3.3%). For [IP3] = 20 nM only 10 of 166 events lasted longer than 3 s (6.0%). For [IP3] = 80 nM, 72 of 309 events lasted longer than 3 s (23%). Error bars denote the sampling error of the histogram. The inset shows the average event duration and its standard deviation.

Mentions: Fig. 3 shows the distribution of event durations for different [IP3], as well as the average event duration depending on [IP3]. For all IP3 concentrations, the majority of events ( 60%) was shorter than one second. However, while for low [IP3] all events are shorter than 3 s, for increasing [IP3] the distribution develops a wide shoulder. This results in a qualitative change in the distribution accompanied by increased average and increased variance of event durations (Fig. 3 inset). Interestingly, models of release termination by inhibiting Ca2+ binding would suggest that larger release amplitudes could only accelerate termination [42]. However, in Fig. 3 we observe both, larger amplitudes and lifetimes, at higher [IP3]. To understand this behavior we will now study the IP3 binding to the receptors.


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)

Distribution of event durations for [IP3] of 10 nM (red bars), 35 nM (green bars) and 70 nM (blue bars).For [IP3] = 10 nM only 3 of 90 events lasted longer than 2 s (3.3%). For [IP3] = 20 nM only 10 of 166 events lasted longer than 3 s (6.0%). For [IP3] = 80 nM, 72 of 309 events lasted longer than 3 s (23%). Error bars denote the sampling error of the histogram. The inset shows the average event duration and its standard deviation.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003965-g003: Distribution of event durations for [IP3] of 10 nM (red bars), 35 nM (green bars) and 70 nM (blue bars).For [IP3] = 10 nM only 3 of 90 events lasted longer than 2 s (3.3%). For [IP3] = 20 nM only 10 of 166 events lasted longer than 3 s (6.0%). For [IP3] = 80 nM, 72 of 309 events lasted longer than 3 s (23%). Error bars denote the sampling error of the histogram. The inset shows the average event duration and its standard deviation.
Mentions: Fig. 3 shows the distribution of event durations for different [IP3], as well as the average event duration depending on [IP3]. For all IP3 concentrations, the majority of events ( 60%) was shorter than one second. However, while for low [IP3] all events are shorter than 3 s, for increasing [IP3] the distribution develops a wide shoulder. This results in a qualitative change in the distribution accompanied by increased average and increased variance of event durations (Fig. 3 inset). Interestingly, models of release termination by inhibiting Ca2+ binding would suggest that larger release amplitudes could only accelerate termination [42]. However, in Fig. 3 we observe both, larger amplitudes and lifetimes, at higher [IP3]. To understand this behavior we will now study the IP3 binding to the receptors.

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