Hierarchical clustering of ryanodine receptors enables emergence of a calcium clock in sinoatrial node cells

Video 7.
The “coupled clock” function in 3-D SANC model. Simulations of local cytosolic calcium dynamics within outer shell and in a cell cross section performed using a 3-D SANC model spontaneously firing action potentials (red curve). Rising diastolic calcium release consists of multiple propagating LCR events that expand by recruitment of couplons that increases NCX current (green curve). L-type current (blue curve) triggers release by a local control mechanism in each couplon, simultaneously depleting the JSR in all couplons, thereby resynchronizing the clocks. See Results for further details and Figs. 18 and 19. The cytosolic [Ca²⁺] is coded by red shades from 0.1 µM (black) to 5 µM (saturation). JSR [Ca²⁺] is coded by cyan color (1,000 µM saturation, 650 µM black). k_NCX = 45 pA/pF and P_up = 24 mM/s.