Fig. 1.

Ion channel modulation during phenotypic switching of VSMC. In contractile VSMC, extracellular Ca²⁺ enters the cell mainly through L-type Ca²⁺ channels and Ca²⁺ release occurs through RyR. Vasoactive agonists, by binding to their receptors, mediate Ca²⁺ release from the ER through IP3R and Ca²⁺ entry via TRPC. Intracellular Ca²⁺ maintains precise control of its own homeostasis through regulation of K⁺, Cl⁻, and Ca²⁺ release channels and Ca²⁺ pumps. Ca²⁺ regulates VSMC contraction through activation of myosin light chain kinase (MLCK) which leads to myosin light chain (MLC) phosphorylation (MLC-P). Vascular tissue injury is associated with a modulation of ion channels, pumps and Ca²⁺-binding proteins and phenotype modulation to a proliferative synthetic phenotype. Na_v voltage-dependent Na⁺ channel; K_v1.5 voltage-dependent K⁺ channel; ClC₃ voltage dependent Cl⁻ channel; VDCC voltage-dependent Ca²⁺ channel; CaM calmodulin