Spatiotemporal orchestration of calcium-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop
Fig 3
Experimental data supports model predictions of in- and inversely out-of-phase Ca2+-cAMP oscillations.
(A) Schematic of the dependence of time delay between Ca2+ and cAMP on the interplay between active AC and PDE. The arrow thickness indicates the regulation strength: the thicker the arrow is, the stronger the regulation is. On the AKAP/AC nanodomain, the active AC dominates, driving the in-phase Ca2+-cAMP oscillation. However, the active PDE dominates outside the AKAP/AC nanodomain, leading to inversely out-of-phase Ca2+-cAMP oscillation. (B) The experimentally observed in-phase Ca2+-cAMP oscillation on the AKAP/AC nanodomain and inversely out-of-phase Ca2+-cAMP oscillation outside the AKAP/AC nanodomain. The in-phase Ca2+-cAMP oscillation is illustrated by the same cAMP peak time and Ca2+ peak time; the inversely out-of-phase Ca2+-cAMP oscillation is indicated by the same cAMP peak time and Ca2+ trough time. These peak or trough time data (circular makers) are from Tenner et al., eLife, 2020 [32], and the black line denotes the diagonal line.