Sarcoplasmic Reticulum Structure and Functional Properties that Promote Long-Lasting Calcium Sparks

Biophysical Journal
Daisuke SatoDonald M Bers

Abstract

Calcium (Ca) sparks are the fundamental sarcoplasmic reticulum (SR) Ca release events in cardiac myocytes, and they have a typical duration of 20-40 ms. However, when a fraction of ryanodine receptors (RyRs) are blocked by tetracaine or ruthenium red, Ca sparks lasting hundreds of milliseconds have been observed experimentally. The fundamental mechanism underlying these extremely prolonged Ca sparks is not understood. In this study, we use a physiologically detailed mathematical model of subcellular Ca cycling to examine how Ca spark duration is influenced by the number of functional RyRs in a junctional cluster (which is reduced by tetracaine or ruthenium red) and other SR Ca handling properties. One RyR cluster contains a few to several hundred RyRs, and we use a four-state Markov RyR gating model. Each RyR opens stochastically and is regulated by cytosolic and luminal Ca. We varied the number of functional RyRs in the single cluster, diffusion within the SR network, diffusion between network and junctional SR, cytosolic Ca diffusion, SERCA uptake activity, and RyR open probability. For long-lasting Ca release events, opening events within the cluster must occur continuously because the typical open time of the RyR is only a ...Continue Reading

References

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Feb 2, 2013·Journal of Molecular and Cellular Cardiology·Dirk Gillespie, Michael Fill

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Citations

Aug 12, 2017·The Journal of General Physiology·Eric A SobieW J Lederer
Feb 14, 2019·Journal of Cellular and Molecular Medicine·Li ZhangZhigang Hu
Mar 9, 2018·Royal Society Open Science·Xudong ChenWenchang Tan
Jul 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Anna V MaltsevMichael D Stern

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