PI(4,5)P₂ reaction model and channel gating models (DG and SPD) used for simulations. (A) Minimal PI(4,5)P₂–DAG reaction scheme (top). Hydrolysis of PI(4,5)P₂ (local) is the first step in this model (k_i). The produced DAG can serve as a substrate for DAG kinase, DAG lipase, and DAG acetyltransferase. For simplicity, we refer only to DAG kinase (k_ii). PA, phosphatidic acid. Further catalytic steps for the producing of CDP-DAG and PI were bound to directly generate PI(4)P (k_iii). The PI(4,5)P₂ recovery from PI(4)P by PIP5K is referred to as “k_iv”. PI(4,5)P₂ and DAG concentrations are linked to the three-state DG (bottom left) and the four-state SPD (bottom right) models. (B) Comparison of TRPC6 current data processed through the DG and SPD simulation models with parameters of the accelerated PLC kinetics. The top panel shows that a rapid decay of TRPC6 current was seen with the SPD model (red trace), but not with the DG model (orange trace). The current amplitudes were normalized to their peak currents (Norm.current). The bottom panel shows the simulated dynamics of PI(4,5)P₂ (solid line) and DAG (dashed line) concentrations.