X. Wu et al., MODULATION OF CALCIUM CURRENT IN ARTERIOLAR SMOOTH-MUSCLE BY ALPHA(V)BETA(3) AND ALPHA(5)BETA(1) INTEGRIN, The Journal of cell biology, 143(1), 1998, pp. 241-252
Vasoactive effects of soluble matrix proteins and integrin-binding pep
tides on arterioles are mediated by alpha(v)beta(3) and alpha(5)beta(1
) 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 afte
r application of soluble cyclic RGD peptide, vitronectin (VN), fibrone
ctin (FN), either of two anti-beta(3) integrin antibodies, or monovale
nt beta(3) antibody. With VN or beta(3) antibody coated onto microbead
s and presented as an insoluble ligand, current was also inhibited. In
contrast, beads coated with FN or alpha(5) antibody produced signific
ant enhancement of current after bead attachment. Soluble alpha(5) ant
ibody had no effect on current but blocked the increase in current evo
ked by FN-coated beads and enhanced current when applied in combinatio
n with an appropriate IgG. The data suggest that alpha(v)beta(3) and a
lpha(5)beta(1) integrins are differentially linked through intracellul
ar signaling pathways to the L-type Ca2+ channel and thereby alter con
trol 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.