The interaction of extracellular calcium with the platelet membrane glycoprotein IIb-IIIa complex.
Platelet aggregation requires the presence of extracellular Ca2+ and fibrinogen. When platelets are activated, fibrinogen receptors become expressed on the cell surface. These receptors are composed of a heterodimer complex of two integral membrane glycoproteins, IIb and IIIa. The requirement for Ca2+ in platelet aggregation can be explained in part by the interaction of Ca2+ with this complex. Conceptually, this interaction can be divided into three parts. First, Ca2+ holds the membrane IIb-IIIa complex together. Half-maximal dissociation of the complex occurs at 37 degrees in the presence of 0.4 uM extracellular Ca2. Mg2+ ions are unable to serve as a substitute for Ca2+. Second, studies with a complex-specific monoclonal antibody that binds only to activated platelets indicate that Ca2+ also is required for the agonist-induced conversion of the IIb-IIIa complex into a functional fibrinogen receptor. The KCa for receptor expression is also 0.4 uM, and Mg2+ is unable to substitute for the Ca2+. Third, Ca2+ is required for the actual binding of fibrinogen to its receptor. In this case, the KCa is 10-100 uM, and Mg2+ is an effective substitute for Ca2+. Thus, Ca2+ holds the IIb-IIIa complex together, is involved in fibrinogen receptor expression and supports fibrinogen binding. These multiple interactions of extracellular Ca2+ with glycoproteins IIb and IIIa help to explain the known requirement for Ca2+ in platelet aggregation.
D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism
D006023:Glycoproteins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D005340:Fibrinogen; D002118:Calcium