Modulation of Calcium Current in Arteriolar Smooth Muscle by α_vβ₃ and α₅β₁ Integrin Ligands

Vasoactive effects of soluble matrix proteins and integrin-binding peptides on arterioles are mediated by α_vβ₃ and α₅β₁ integrins. To examine the underlying mechanisms, we measured L-type Ca²⁺ channel current in arteriolar smooth muscle cells in response to integrin ligands. Whole-cell, inward Ba²⁺ currents were inhibited after application of soluble cyclic RGD peptide, vitronectin (VN), fibronectin (FN), either of two anti–β₃ integrin antibodies, or monovalent β₃ antibody. With VN or β₃ antibody coated onto microbeads and presented as an insoluble ligand, current was also inhibited. In contrast, beads coated with FN or α₅ antibody produced significant enhancement of current after bead attachment. Soluble α₅ antibody had no effect on current but blocked the increase in current evoked by FN-coated beads and enhanced current when applied in combination with an appropriate IgG. The data suggest that α_vβ₃ and α₅β₁ integrins are differentially linked through intracellular signaling pathways to the L-type Ca²⁺ channel and thereby alter control of Ca²⁺ influx in vascular smooth muscle. This would account for the vasoactive effects of integrin ligands on arterioles and provide a potential mechanism for wound recognition during tissue injury.