As second messengers, calcium ions bind several calcium-sensing proteins like calmodulin to generate cellular responses such as muscle contraction, nerve signaling, oocyte fertilization, and T cell activation. Upon GPCR stimulation, phospholipase C-beta signals IP3 to increase cytosolic calcium concentration. The binding of one calcium ion to calmodulin helps three additional calcium ions bind and induce a conformational change. The active calcium-calmodulin complex can now bind target proteins with high affinity. For example, when the calcium concentration in the cell is high, the calcium-calmodulin complex binds calcium pumps on the plasma membrane to release excess ions. Additionally, calcium-calmodulin also affects other second messenger–mediated pathways, such as the cyclic AMP signaling pathway. It binds and activates phosphodiesterase to degrade cyclic AMP to 5-prime-AMP, thereby inhibiting its effect on protein kinase A.