Modulation of calcium current in arteriolar smooth muscle by alphav beta3 and alpha5 beta1 integrin ligands.
Vasoactive effects of soluble matrix proteins and integrin-binding peptides on arterioles are mediated by alphav beta3 and alpha5 beta1 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-beta3 integrin antibodies, or monovalent beta3 antibody. With VN or beta3 antibody coated onto microbeads and presented as an insoluble ligand, current was also inhibited. In contrast, beads coated with FN or alpha5 antibody produced significant enhancement of current after bead attachment. Soluble alpha5 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 alphavbeta3 and alpha5 beta1 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.
Wu
X
X
Microcirculation Research Institute and Departments of Medical Physiology, Texas A & M University Health Science Center, College Station, Texas 77843-1114, USA.
Mogford
J E
JE
Platts
S H
SH
Davis
G E
GE
Meininger
G A
GA
Davis
M J
MJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001160:Arterioles / Q000166:cytology / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D005353:Fibronectins / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D017469:Receptors, Fibronectin / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019096:Vitronectin / Q000494:pharmacology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D005353:Fibronectins; C085636:GpenGRGDSPCA; D007074:Immunoglobulin G; D009842:Oligopeptides; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D019096:Vitronectin