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Daisuke Sato, Thomas R. Shannon, Donald M. Bers  Biophysical Journal 

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Presentation on theme: "Daisuke Sato, Thomas R. Shannon, Donald M. Bers  Biophysical Journal "— Presentation transcript:

1 Sarcoplasmic Reticulum Structure and Functional Properties that Promote Long-Lasting Calcium Sparks 
Daisuke Sato, Thomas R. Shannon, Donald M. Bers  Biophysical Journal  Volume 110, Issue 2, Pages (January 2016) DOI: /j.bpj Copyright © 2016 Biophysical Society Terms and Conditions

2 Figure 1 (A) Schematic illustration of the network SR. (B) Regular Ca spark. Typical spark duration is ∼20– 40 ms. The number of RyRs = 100. To see this figure in color, go online. Biophysical Journal  , DOI: ( /j.bpj ) Copyright © 2016 Biophysical Society Terms and Conditions

3 Figure 2 RyR cluster size (number of functional RyRs per cluster) and Ca spark duration. (A) Mean spark duration versus the number of RyRs, which peak at near 40. Solid line, spark duration based on RyR opening. Sparks occurred naturally from the stochastic nature of RyR gating and thus give standard deviations shown with error bars. Dashed line, spark duration based on full-duration at half maximum (FDHM) of Ca transients. (B) Short spark where stochastic attrition terminates SR Ca release (for 10 RyRs). (C) Short spark where [Ca]jsr depletion terminates SR Ca release (300 RyRs). (D) Long-lasting spark with 40 RyRs and [Ca]jsr remaining >600 μM. (E) Histograms of Ca spark duration for 100 and 40 RyR clusters. To see this figure in color, go online. Biophysical Journal  , DOI: ( /j.bpj ) Copyright © 2016 Biophysical Society Terms and Conditions

4 Figure 3 Ca diffusion and spark duration. (A) Mean spark duration versus τnsr. x axis is relative value and both τnsrL and τnsrT are rescaled with respect to the original values. Sparks occurred naturally from the stochastic nature of RyR gating and thus give standard deviations shown with error bars. (Inset) The effect of diffusion between the network SR and the junctional SR and spark duration. Mean spark duration versus diffusion between the network SR and the junctional SR (τnsr-jsr) for 100 RyRs. (B) Extremely long-lasting (∼1 s) Ca release event. τnsr = 0.5 (relative). (C) Cytosolic Ca diffusion and spark duration. Mean spark duration versus diffusion between submembrane space and bulk cytosolic space (τsi) for 100 RyRs. (D) Cytosolic Ca diffusion and spark duration. Mean spark duration versus cytosolic Ca diffusion (τi). x axis is relative value and both τiL and τiT are rescaled with respect to the original values (100 RyRs). To see this figure in color, go online. Biophysical Journal  , DOI: ( /j.bpj ) Copyright © 2016 Biophysical Society Terms and Conditions

5 Figure 4 The SERCA pump, RyR, and spark duration. (A) Mean spark duration versus kup (left axis) and [Ca]SR versus kup (right axis). The number of RyRs = 100. (Inset) Mean spark duration versus [Ca]SR using the same data. (B) Ultra-long (∼2 s) Ca spark. kup = 0.74 (relative). (C) Mean spark duration versus initial SR Ca load. (D) Open probability and spark duration. Mean spark duration versus kclosed→open. The number of RyRs = 100. (E) Effect of the conductance of the single RyR on spark duration. The spark duration versus the single RyR conductance. The number of RyRs = 100. (F) Single RyR conductance versus the number of RyRs versus spark duration. Both of them have biphasic effect. To see this figure in color, go online. Biophysical Journal  , DOI: ( /j.bpj ) Copyright © 2016 Biophysical Society Terms and Conditions

6 Figure 5 Effect of multiple factors. (A) Black curve: the spark duration versus the number of RyRs with moderate [Ca]SR. [Ca]SR was reduced by increasing nonspecific SR Ca leak (gleak = 4.14 × 10−5 μM/ms). [Ca]SR = 906 μM. Red curve, the spark duration versus the number of RyRs with higher [Ca]SR. gleak = 0 and [Ca]SR = 1150 μM; green curve, fast diffusion. Diffusion between the network SR and the junctional SR (τnsr) was decreased (τnsr × 0.8 from the red and black curves). Dashed lines, RyR sensitivity was decreased. (kclosed→open × 0.8). (B) Black curve, the spark duration versus the number of RyRs with moderate [Ca]SR ([Ca]SR = 1150 μM); red curve, the spark duration versus the number of RyRs with higher [Ca]SR ([Ca]SR = 1356 μM). SERCA was upregulated. Green curve, SERCA upregulation + fast diffusion. Diffusion between the network SR (τnsr) was decreased (τnsr is half from the red and black curves). Dashed lines, RyR sensitivity was decreased. (kclosed→open × 0.8). To see this figure in color, go online. Biophysical Journal  , DOI: ( /j.bpj ) Copyright © 2016 Biophysical Society Terms and Conditions


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