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© The Rockefeller University Press, 0021-9525/1998//241 $5.00
The Journal of Cell Biology, Volume 143, Number 1, , 1998 241-252

Modulation of Calcium Current in Arteriolar Smooth Muscle by _vβ₃ and ₅β₁ Integrin Ligands

Xin Wu^*, Jon E. Mogford^*, Steven H. Platts^*, George E. Davis, Gerald A. Meininger^*, and Michael J. Davis^*

^* Microcirculation Research Institute and Departments of Medical Physiology, Pathology and Laboratory Medicine, Texas A & M University Health Science Center, College Station, Texas 77843-1114

Vasoactive effects of soluble matrix proteins and integrin-binding peptides on arterioles are mediated by _vβ₃ and ₅β₁ 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 ₅ antibody produced significant enhancement of current after bead attachment. Soluble 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 _vβ₃ and ₅β₁ 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.

Key Words: voltage-gated Ca²⁺ channel • vascular smooth muscle • wound repair • extracellular matrix • integrin-mediated signaling

Abbreviations used in this paper: ECM, extracellular matrix; F11, β₃ integrin monoclonal antibody; FAK, focal adhesion kinase; FN, fibronectin; HM5-1, ₅ integrin monoclonal antibody; I_Ba, whole-cell Ba²⁺ current; MHC, anti–rat IgG monoclonal antibody; PSS, physiological saline solution; SMC, smooth muscle cell(s); VN, vitronectin.

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