Fig 2. Idealized partialDE model demonstrating cAMP generation and diffusion (diffusion coefficient 300 μm²/s) from t-tubular caveolar microdomains (seen as rectangles along edge of inset) at various time points following β₁AR stimulation with 30 nM isoproterenol (basal cAMP = 0.1 μM).

(A) As expected, in the absence of PDEs or anatomical barriers, diffusion is rapid with miniscule gradients and cAMP concentration grows unboundedly. (B) To simulate effects of PDEs, experimentally measured concentrations of PDEs were added into caveolar microdomains (10 PDE molecules/cavelor domain), and (C) Effect of 10-fold increase in the concentration of PDEs. No gradients were observed. (D) When diffusion coefficient was set to 60 μm²/s, the simulated results showed sub-nanomolar gradients before 1.0 second. (E) Diffusion coefficient was set to 10 μm²/s. Miniscule gradients (sub-nanomolar) were observed during the early time periods (before 1.0 second) when concentration of PDE was increased 10 fold.