Modulation of calcium current in arteriolar smooth muscle by αvβ3 and α5β1 integrin

Vasoactive effects of soluble matrix proteins and integrin-binding peptides on arterioles are mediated by alpha(v)beta(3) and alpha(5)beta(1) integrins. To examine the underlying mechanisms, we measured L-type Ca(2+) channel current in arteriolar smooth muscle cells in response to integrin ligands. Whole-cell, inward Ba(2+) currents were inhibited after application of soluble cyclic RGD peptide, vitronectin (VN), fibronectin (FN), either of two anti-beta(3) integrin antibodies, or monovalent beta(3) antibody. With VN or beta(3) antibody coated onto microbeads and presented as an insoluble ligand, current was also inhibited. In contrast, beads coated with FN or alpha(5) antibody produced significant enhancement of current after bead attachment. Soluble alpha(5) 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 alpha(v)beta(3) and alpha(5)beta(1) integrins are differentially linked through intracellular signaling pathways to the L-type Ca(2+) channel and thereby alter control of Ca(2+) 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.