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. 2019 Dec 27;39(4):e102723. doi: 10.15252/embj.2019102723

Figure 4. Discrete‐event simulations of cGMP dynamics.

Figure 4

  1. Schemes illustrate three different situations defined by chemical reactions (2) to (5) in the Materials and Methods section. Colors of schemes refer to the simulations shown in panel (B).
  2. Characteristic decay of V m in experiments shown in Fig 3A and C (orange; τrelax = 0.384 s) is compared with cGMP hydrolysis by PDE5 in the absence of CNGK channels (blue; characteristic time τ = 0.131 s), dissociation of cGMP from CNGK at the rate k off (yellow; τ = 0.748 s), and cGMP hydrolysis in the presence of CNGK channels and PDE (violet; τ = 9.73 s). Simulations were done using those parameters listed in Appendix Table S3. cGMP is given in molecules.
  3. Simulations of the rate of cGMP hydrolysis upon varying the catalytic rate k cat of active PDE and the k on rate of cGMP binding to the CNBD of the CNGK channel. The gray plane indicates the experimental relaxation time (τrelax). The black dot represents k cat (24/s) and k on (5.2 × 107/M/s) compatible with previous studies (Appendix Table S3). The pairs of parameters compatible with the experimental τrelax are positioned at the intersection of the colored surface and the gray plane.
  4. Top view of panel C showing k off values compatible with k on rates used for simulations (assuming K D,CNGK = 25.7 nM; see Appendix Table S3).