Movement of Calcium Ions and their Role in the Activation of Platelets

Abstract

SummaryThe increase of the cytoplasmic Ca-concentration plays a central role in the initiation of platelet activation. Four kinds of movements of Ca-ions are presumed to occur during this process: a) Ca-ions liberated from membranes induce the rapid shape change, b) Vesicular organelles release Ca-ions into the cytoplasm which initiate the release reaction, c) The storage organelles called dense bodies, secrete their contents including Ca-ions to the outside during the release reaction, d) At the same time a rearrangement of the plasma membrane occurs, resulting in an increase in its permeability for Ca-ions as well as in an increase in the number of Ca-binding sites.Since most processes occurring during platelet activation are reversible, the platelet must be equipped with a mechanism which removes Ca-ions from the cytoplasm. A vesicular fraction obtained from homogenized platelets indeed accumulates Ca actively. This Ca- pump is stimulated by cyclic AMP and protein kinase; it may be involved in the recovery of platelets after activation.It becomes increasingly clear that the various manifestations of platelet activation are triggered by a rise in the cytoplasmic Ca2+-concentration. The evidence for this and possible mechanisms involved are discussed in some detail in the contributions by Detwiler et al. and by Gerrard and White to this symposium. In this article we shall discuss four different types of mobilization of Ca-ions which occur in the course of the activation of platelets. In addition, at least one transport step involved in the removal of Ca2+ must occur during relaxation of activated platelets.

Relationship between structure of phenothiazine analogues and their activity on platelet calcium fluxes

“…Non-phenothiazine drugs such as TMB8 which inhibits internal calcium release (Chiou & Malagodi, 1975) were much less potent than phenothiazines. Further, we observed an apparent correlation between the phenothiazine-induced inhibition of platelet activation and calcium uptake, both phenomena being calcium-dependent (Detwiler et al, 1978;Massini et al, 1978;Levy-Toledano etal., 1982).…”

“…It is generally recognized that calcium ions play a key role in the regulation of platelet function (Detwiler et al, 1978;Massini et al, 1978). We have shown previously that in response to the calcium ionophore A 23187, ethylene diaminetetraacetic acid (EDTA)-treated platelets undergo an increase in light transmission.…”

“…One of the main storage pools of calcium in the platelet is the dense tubular system (Massini et al, 1978). This system is similar to the muscular sarcoplasmic reticulum which is able to incorporate and liberate calcium.…”

Platelet cryopreservation using a trehalose and phosphate formulation

“…The increase of cytosolic calcium concentration is an integral step in the platelet activation and aggregation mechanism (Jackson et al, 2003;Massini et al, 1978). Using Fura-2 loaded into the platelet cytosol, we measured the cytosolic calcium concentration changes in cryopreserved platelets and compared them with those in fresh platelets.…”

Biochemical mechanisms in 5-hydroxytryptamine-induced human platelet aggregation

“…Increase of the intracellular free calcium plays a central role in the regulation of postreceptor events leading to platelet activation, morphologically expressed as shape change reversible aggregation and release reaction [24,25]. As for other agonists, 5-HT induces an increase of the concentration of free calcium in the cytoplasm [8].…”