Spatiotemporal orchestration of calcium-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop
Fig 2
Phase oscillations of Ca2+ and cAMP are driven by active AC and PDE.
(A) The simulation domain and initial condition of AC and AKAP. The compartment and the assumption of one AKAP/AC nanodomain are the same as those in [32]. (B) The time delay between Ca2+ and cAMP as a function of the distance x to the AKAP/AC nanodomain. The time delay is defined as the difference of peak time between Ca2+ and cAMP. (C) The non-normalized dynamics of Ca2+ and cAMP at x = 0, 40, 49, 60, 200 nm. The vertical dashed lines label the time when cAMP achieves the peak. The blue color indicates the value of x: the lighter the blue is, the larger the x is. (D) The normalized dynamics of Ca2+ (in red) and cAMP (in blue) at x = 0 nm (upper panel), x = 49 nm (middle panel), and x = 200 nm (lower panel). (E) Kymographs depicting the dynamics for Ca2+, active AC (AC*), and active PDE (PDE*) at different locations at the cell membrane. The x coordinate is the time, and the y coordinate is the distance x present in (B). Trough time and peak are indicated by a plus sign and triangle, respectively. Here, the peak time is the time when the concentration of species reaches the maximal value, and the trough time the minimal value. (F) Comparisons between Ca2+ trough time and AC* trough time (left; plus sign), between Ca2+ peak time and AC* peak time (left; triangle), between Ca2+ trough time and PDE* trough time (right; plus sign), and between Ca2+ peak time and PDE* peak time (right; triangle). The diagonal line indicates the equality of the x-axis and y-axis. (G) Kymograph depicting cAMP dynamics. The color intensity indicates the normalized cAMP level. The plus sign and triangle denote the cAMP peak time when x is large and small, respectively. (H) Comparisons between AC* peak time and cAMP peak time on the AKAP/AC nanodomain (left), and between PDE* trough time and cAMP peak time outside the AKAP/AC nanodomain (right).