Fig. 4.

Simulations show that including the identified parallel adaptive feedback loops into the model markedly enhances the reliability of the Ca²⁺ signaling system in response to changes in the synthesis rates of signaling components. (A) Marked stabilization of both basal cytosolic and ER Ca²⁺ levels (gray box). (B) Parallel adaptive feedback is well suited to preserve the setpoints where receptor stimuli first triggered Ca²⁺ oscillations and first triggered a plateau phase. Instead of the marked reduction in the range over which oscillations occurred in the model without adaptive feedback (from Fig. 1C), the signaling system with adaptive feedback (gray box) now shows minimal changes in the responsiveness to receptor stimulation.