The Interplay of Rogue and Clustered Ryanodine Receptors Regulates Ca2+ Waves in Cardiac Myocytes

Figures

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  Figure 1. Schematic illustration of the 2D model for Ca2+ waves. (A) Schematic representative of the 2D geometrical model of a cardiac myocyte. The yellow circles denote JSRs. The spacing intervals between JSRs: lx = 2 μm and ly = 0.8 μm. (B) Schematic representative of two JSRs, which include randomly distributed clustered and rogue RyRs (l = 0.1 μm). (C) A flow diagram for the Monte Carlo simulations.

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  Figure 2. Interplay of rogue and clustered RyRs in neighbor JSRs. Snapshots of Ca2+ release events in a computational region of 20 × 20 μm2 were taken at 10, 20, and 40 ms from left to right when a CRU of clustered RyRs was fired. (A) Rogue RyRs in a neighbor JSR are activated. (B) Clustered RyRs in a neighbor JSR are initiated by a Ca2+ spark directly. (C) Clustered RyRs are triggered with the help of rogue RyRs.

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  Figure 3. Properties of Ca2+ waves. (A) The probability of inducing Ca2+ waves triggered by different numbers of Ca2+ sparks. (B) The number of triggered Ca2+ sparks in 100 ms.

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  Figure 4. Ca2+ waves triggered by four sparks at the corner of a computational domain, i.e., (18, 19.2), (18, 18.4), (18, 17.6), (18, 16.8) in the region of 20 × 20 μm2. The beginning level of [Ca2+]lumen is 1.0 mM. (A,B) Snapshots of Ca2+ waves initially triggered by Ca2+ sparks with rogue RyRs (A) and without considering rogue RyRs (B) at 10, 50, 100, 150 ms from left to right. (C) Computational results for line-scan images of [Ca2+]cyto with and without rogue RyRs at the line of y = 16.8.

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  Figure 5. Ca2+ waves under different [Ca2+]lumen. (A) Computational results for line-scan images of [Ca2+]cyto at the line of y = 16.8 when [Ca2+]lumen = 0.3, 0.6, and 0.9 mM. (B) The longitudinal velocity of Ca2+ waves affected by [Ca2+]lumen. (C) The amplitude of Ca2+ waves affected by [Ca2+]lumen.

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  Figure 6. Effects of CRU number of rogue RyRs in a JSR on wave propagation. (A) Computational results for line-scan images of [Ca2+]cyto at the line of y = 16.8 when CRU number of rogue RyRs has values of 2, 8, and 14. (B) The amplitude and longitudinal velocity of Ca2+ waves when Nrogue varies from 2 to 14.

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  Figure 7. The amplitude and longitudinal velocity of Ca2+ waves when l varies from 0.05 to 0.2 μm.