Migration of human vascular smooth muscle cells involves serum-dependent repeated cytosolic calcium transients

Migration of vascular smooth muscle cells (VSMC) is a key event in the form ation of neointima during atherosclerosis, Fura-2 loaded VSMCs were used to investigate calcium homeostasis during cell migration. Multiple spontaneou s transient increases in cytosolic free calcium [Ca2+](i) were observed in single human VSMCs migrating on type I collagen. Such [Ca2+](i) transients were dependent on the presence of serum or PDGF-BB. Removal of serum, or lo ading cells with BAPTA, abolished the transients and decreased cell migrati on speed. The transients were not affected by disruption of cell polarizati on by dihydrocytochalasin B, Adhesion was used to investigate the specific role of cell-substrate interactions in the generation of transients, Transi ents are seen in VSMCs adhering either on collagen or on poly-L-lysine, sug gesting that generation of transients is not strictly dependent on integrin s. Buffering [Ca2+](i) with BAPTA led to accumulation of pr integrins at th e cellular tail, and to increased release of integrin on the extracellular matrix. These results demonstrate a role for [Ca2+](i) transients in the ra pid, serum-dependent migration of VSMCs, These [Ca2+](i) transients are pre sent in migrating VSMCs only when two simultaneous events occur: (1) substr ate independent spreading and (2) stimulation of cells by serum components such as PDGF-BB.