Figure 6.

Detailed kinetic model of NOS-G with its multi-loop positive feedback control and input signaling axes. Here, various types of activation and inhibition are indicated as arrows and dotted lines with symbol T, respectively. The family of nested positive feedback loops is depicted as blue arrows numbered 1 to 8 (in blue circles). The positive feed forward loop, based on the phosphorylation of RyR with PKG1, has the number 9. Negative feedbacks (marked by black circles and shown in red) are numbered 10 through 12. Crosstalk loops, describing the positive impact of AC/cAMP/PKA-signaling axis on NOS-RG (on PKB, ARC, and RyR), have the numbers 13 through 15. Various hormones (with corresponding receptors), activating G-proteins and RTKs, are placed in the boxes. Known effects of PKG1 on Ca²⁺-pumps SERCA and PMCA and activation/inhibition of phosphodiesterases II/III by PKG1 are omitted for simplicity. Description of this model and other details are given in the text.