17 - Platelet signalling: calcium

Summary

Introduction

An increase in the cytosolic calcium concentration [Ca²⁺]_i is a major signal underlying platelet activation. Physiological agonists increase the [Ca²⁺]_i by stimulating both the release of Ca²⁺ from intracellular stores in the endoplasmic reticulum (ER) and the entry of Ca²⁺ across the plasma membrane (PM). After stimulation, the [Ca²⁺]_i can be reduced by sequestration of Ca²⁺ into the ER and extrusion across the PM. The Ca²⁺ -ATPases responsible also maintain the [Ca²⁺]_i around 30–50 nM in resting platelets by working against the leakage of Ca²⁺ into the cytosol from the ER and across the PM.

The release of stored Ca²⁺

Most platelet agonists are able to release stored Ca²⁺ from the ER (the dense tubular system of platelets). The occupation of surface receptors results in the activation of phospholipase C (PLC) and so the formation of the Ca²⁺ releasing messenger, inositol 1, 4, 5-trisphosphate (IP₃), which acts on receptors on the ER. Many platelet agonists, including ADP, platelet activating factor (PAF), thrombin and thromboxane A₂, have been shown to activate PLC-β₁ via a heterotrimeric GTP-binding protein3. PAF and thrombin also appear to activate PLC-γ₁, and thrombin and collagen activate PLC-γ₂.

Platelets are reported to express three isoforms of the IP₃ receptor (IP₃R): IP₃R types I, II and III. IP₃RI has been located in the intracellular membranes, in contrast to IP₃RIII which has been found exclusively at the PM. The IP₃RII has been found associated with both internal membranes and the PM.