Histophysiology of the circulating platelet.

The role of platelets in hemostasis and thrombosis has been well established since Eberth's and Schimmelbusch's pioneering intravital microscopic experiments. A century ago the distinct features of the circulating "smooth disc" and the activated "spiny sphere" were described. Since then the underlying cell-biological processes transforming a harmless floating platelet into a sticky corpuscle, ready to release its stores of thrombogenic and atherogenic substances have been unveiled. However, its life-threatening capabilities have evolved from the necessity of preventing equally dangerous blood losses from a pressurized circulation system. As circulation depends on the liquid state of blood, the platelets and the molecules of the plasmatic coagulation system must circulate in an inactive state, to become activated at the site of "demand" to transform the liquid into a solid hemostatic plug. As in nucleated cells the plasma membrane, made up of a phospholipid bilayer with integrated glycoproteins, is the structure signalling environmental information to the platelet interior. Many of the receptors for stimulatory or inhibitory mediators elicit a cell-biological response via G-proteins and subsequent Ca2+ mobilization by IP3, or stimulation/inhibition of adenylate cyclase followed by changes in cytoplasmic levels of cyclic AMP. The supposed intracellular Ca2+ store of the platelets, the dense tubular system, also appears as the site of Ca2(+)-activated prostaglandin synthesis. Raised cytoplasmic Ca2+ levels promote the polymerization of G-actin to F-actin involved in the extension of pseudopodia in the course of "external shape change." Ca2(+)-activated myosin light-chain kinase phosphorylates myosin which becomes associated with F-actin, with the resulting acto-myosin complex providing the contractile force for "internal shape change," i.e., the centralization of organelles and for clot retraction later in hemostasis. More than by the three-dimensional actin cytoskeleton proper, the discoid shape typical of the nonstimulated platelet appears to be secured by a two-dimensional membrane skeleton of actin filaments anchored to membrane glycoproteins via actin-binding protein or spectrin and ankyrin. Although the microtubule coil has been confirmed as the main determinant of the mechanical stiffness of the platelet with biophysical techniques, its hitherto assumed role for the maintenance of the disc shape no longer appears tenable. The morphological phenomenon of the shape change comprises an alteration of membrane glycoproteins resulting in binding of "adhesive" molecules like fibrinogen.(ABSTRACT TRUNCATED AT 400 WORDS)