Agonist (A)-receptor (R) interaction increases the hydrolysis of phosphatidylinositol 4,5- bisphosphate (PIP₂) and IP₃ production in VSM. IP₃ stimulates Ca²⁺ release from the sarcoplasmic reticulum (SR). Also, extracellular Ca²⁺ enters VSMC through Ca²⁺ channels. Ca²⁺ binds calmodulin (CaM), which could activate myosin light chain (MLC) kinase and initiate contraction, or regulate the activity of K⁺ channels, Ca²⁺ release channels, Ca²⁺ pumps, and CaM kinase II. During vascular injury, VSMC transforms into undifferentiated phenotype and enters a cell cycle which consists of G₁, growth and preparation of the chromosomes for replication; S, synthesis of DNA; G₂, preparation for mitosis; and M, mitosis. Ca²⁺/CaM increases the activity of cyclin E/CDK2 and stimulates G₁/S transition, and thereby promotes VSM growth and proliferation.