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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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Comparison of inter-wave dynamics for experiments and simulations.(A) shows representative fluorescence traces from 3 puff sites in Xenopus oocyte. Waves were identified as large signals that occurred approximately at the same time at all cluster sites. (B, C): scatter plot of puff amplitudes in experimental (B) and simulated traces (C). The amplitude of a puff is defined by the peak fluorescense for experimental data and the peak number of open channels for simulated data. The horizontal axis is the inter-wave phase with 0 corresponding to the time of the preceding wave and 1 corresponding to the time of the next wave. Experimental data was pooled from four experiments, simulation data was pooled from traces for 60, 70, and 80 nM [IP3]. The amplitudes of experimental and simulated data were then rescaled to their respective mean amplitude. The data was grouped into 10 intervals (shaded regions); filled markers and error bars denote the mean and standard deviation of each group, respectively. (D) Temporal distribution of puff frequency between two waves after binning of data in 0.1 phases. (E) Mean (solid lines with standard error) and standard deviations (dashed lines) of binned amplitudes for simulations (black) and exeriments (gray).
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pcbi-1003965-g008: Comparison of inter-wave dynamics for experiments and simulations.(A) shows representative fluorescence traces from 3 puff sites in Xenopus oocyte. Waves were identified as large signals that occurred approximately at the same time at all cluster sites. (B, C): scatter plot of puff amplitudes in experimental (B) and simulated traces (C). The amplitude of a puff is defined by the peak fluorescense for experimental data and the peak number of open channels for simulated data. The horizontal axis is the inter-wave phase with 0 corresponding to the time of the preceding wave and 1 corresponding to the time of the next wave. Experimental data was pooled from four experiments, simulation data was pooled from traces for 60, 70, and 80 nM [IP3]. The amplitudes of experimental and simulated data were then rescaled to their respective mean amplitude. The data was grouped into 10 intervals (shaded regions); filled markers and error bars denote the mean and standard deviation of each group, respectively. (D) Temporal distribution of puff frequency between two waves after binning of data in 0.1 phases. (E) Mean (solid lines with standard error) and standard deviations (dashed lines) of binned amplitudes for simulations (black) and exeriments (gray).

Mentions: In [11], [24] it was shown that in Xenopus oocytes puffs appear in the phase between succeeding global waves. Exemplary fluorescence traces from experiments with this cell type are shown in Fig. 8A. Here a wave can be identified as a group of large events that appear within temporal proximity at neighboring cluster sites. The remaining events are then identified as puffs and their amplitude has been obtained as peak fluorescence level from traces such as shown in the figure. These amplitudes are plotted in Fig. 8B versus the phase during the IWI, where the phase has been defined as the ratio of time that has passed since the last wave and the total difference between preceding and next wave. Fig. 8C shows for comparison the corresponding puff events from numerical simulations. As seen from Fig. 7, the three data sets for high [IP3] are quite similar, suggesting to pool them for better statistics. It is evident from the two plots, that events are absent at the very early phase after waves and that large-amplitude events occur only towards the end of the interval.


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)

Comparison of inter-wave dynamics for experiments and simulations.(A) shows representative fluorescence traces from 3 puff sites in Xenopus oocyte. Waves were identified as large signals that occurred approximately at the same time at all cluster sites. (B, C): scatter plot of puff amplitudes in experimental (B) and simulated traces (C). The amplitude of a puff is defined by the peak fluorescense for experimental data and the peak number of open channels for simulated data. The horizontal axis is the inter-wave phase with 0 corresponding to the time of the preceding wave and 1 corresponding to the time of the next wave. Experimental data was pooled from four experiments, simulation data was pooled from traces for 60, 70, and 80 nM [IP3]. The amplitudes of experimental and simulated data were then rescaled to their respective mean amplitude. The data was grouped into 10 intervals (shaded regions); filled markers and error bars denote the mean and standard deviation of each group, respectively. (D) Temporal distribution of puff frequency between two waves after binning of data in 0.1 phases. (E) Mean (solid lines with standard error) and standard deviations (dashed lines) of binned amplitudes for simulations (black) and exeriments (gray).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003965-g008: Comparison of inter-wave dynamics for experiments and simulations.(A) shows representative fluorescence traces from 3 puff sites in Xenopus oocyte. Waves were identified as large signals that occurred approximately at the same time at all cluster sites. (B, C): scatter plot of puff amplitudes in experimental (B) and simulated traces (C). The amplitude of a puff is defined by the peak fluorescense for experimental data and the peak number of open channels for simulated data. The horizontal axis is the inter-wave phase with 0 corresponding to the time of the preceding wave and 1 corresponding to the time of the next wave. Experimental data was pooled from four experiments, simulation data was pooled from traces for 60, 70, and 80 nM [IP3]. The amplitudes of experimental and simulated data were then rescaled to their respective mean amplitude. The data was grouped into 10 intervals (shaded regions); filled markers and error bars denote the mean and standard deviation of each group, respectively. (D) Temporal distribution of puff frequency between two waves after binning of data in 0.1 phases. (E) Mean (solid lines with standard error) and standard deviations (dashed lines) of binned amplitudes for simulations (black) and exeriments (gray).
Mentions: In [11], [24] it was shown that in Xenopus oocytes puffs appear in the phase between succeeding global waves. Exemplary fluorescence traces from experiments with this cell type are shown in Fig. 8A. Here a wave can be identified as a group of large events that appear within temporal proximity at neighboring cluster sites. The remaining events are then identified as puffs and their amplitude has been obtained as peak fluorescence level from traces such as shown in the figure. These amplitudes are plotted in Fig. 8B versus the phase during the IWI, where the phase has been defined as the ratio of time that has passed since the last wave and the total difference between preceding and next wave. Fig. 8C shows for comparison the corresponding puff events from numerical simulations. As seen from Fig. 7, the three data sets for high [IP3] are quite similar, suggesting to pool them for better statistics. It is evident from the two plots, that events are absent at the very early phase after waves and that large-amplitude events occur only towards the end of the interval.

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