Figure 1.

Calcium-dependent regulation of vascular smooth muscle cell (VSMC) contraction. Vasoconstrictors induce VSMC contraction by increasing the intracellular levels of Ca²⁺. Vasoactive peptides, such as Ang II, bind to G protein-coupled receptors (GPCRs) activating PLC leading to (i) production of IP₃ and (ii) formation of DAG. IP₃ binds to the IP receptor Ca²⁺ channel (InsP3R) and induces Ca²⁺ release from the sarcoplasmic reticulum (SR). DAG causes activation of PKC, which influences Ca²⁺ channels, such as store-operated Ca²⁺ channel (SOC), second messenger-operated Ca²⁺ channel (SMOC), receptor-operated Ca²⁺ channel (ROC), voltage-gated Ca²⁺ channel (VOC), and the Na⁺–Ca²⁺ exchanger (NCX). PKC also stimulates activity of the ryanodine Ca²⁺ channel (RyR) inducing release of Ca²⁺ from the SR. MLCP activity is reduced by CPI-17 phosphorylation. Ca²⁺ binds to calmodulin and activates the MLCK, leading to MLC20 phosphorylation at Ser19, actin polymerization, and vascular contraction.