Abnormal Calcium Transport Into Microsomes of Gray Platelet Syndrome

Abstract

Gray platelets initially described as lacking α granules also show thrombin-induced aggregation and release lower than normal. One of the possible explanation is a modified intracellular Ca2+ concentration which is involved in platelet activation. We then decided to investigate the relationship between the morphological abnormality and a possible regulation of platelet Ca2+ concentration.We isolated a platelet membrane fraction (100,000 g) enriched in intracellular membranes which actively sequesters Ca2+. This Ca2+ uptake was mediated by a characterized (Ca2+ + Mg2+) ATPase.The isolated membrane vesicles from two patients show an increase in the calcium uptake. The stimulation reaches a factor 2 to 3 agd the Ca2+ uptake appears greatly increased whatever the Ca concentration used. This led us to investigate the Ca2+ + Mg2+ ATPase activity. The enzymatic activity appears increased in the first 10 minutes which correlates with the increased rate in calcium uptake. The specific activity of the enzyme is increased by a factor 2.4 to 2.7 which again agrees with the calcium uptake results. Therefore we suggest that the severe impairment in secretion found in the Gray platelets is probably related to the low cytoplasmic mobilization as it is found by Hardisty et al, 1985 ; this would be the consequence of an increased Ca2+ uptake rather than a decrease in the Ca liberation.The absence of α granules in Gray platelets together with the described abnormality in internal membranes and the recently described modification of external membrane fluidity (Rendu et al 1985) would suggest that these platelets have a general membrane disorder.