Modeling of PIP₂ depletion by M₁R activation. Symbols are data from Jensen et al. (2009), and lines are model predictions. (A–C) KCNQ2/3 current. (D–F) PH probe FRET. (A and D) Time course of current/FRET inhibition by 10 µM Oxo-M. (B and E) Time course of recovery after M₁R activation. (C and F) Concentration–response curves. Parameters for the red, solid curves are as listed in Tables I and II. For the blue, dotted curves, PI kinases and phosphatases were sped up by 10-fold (k_4K, 2.6 × 10⁻³ s⁻¹; k_4P, 0.08 s⁻¹; k_5K, 0.2 s⁻¹; k_5P, 0.14 s⁻¹). For the green, dashed curves, the PI 4-kinase was sped up during Oxo-M (but not during recovery) in a manner depending on Oxo-M concentration (2.6 × 10⁻⁴ s⁻¹ for 0.001 µM, 5 × 10⁻⁴ s⁻¹ for 0.01 µM, and 2.6 × 10⁻³ s⁻¹ for 0.1 µM and above). k_5K was 0.2 s⁻¹ during Oxo-M and 0.02 s⁻¹ during recovery. k_4P and k_5P were not accelerated. k_PLC was 0.2 µm² s⁻¹ to fit onset. PLConPIP was 0.