Cardiovascular and hemostatic disorders: SOCE and Ca2+ handling in platelet dysfunction

Abstract

Among the Ca2+ entry mechanisms in platelets, store-operated Ca2+ entry (SOCE) plays a prominent role as it is necessary to achieve full activation of platelet functions and replenish intracellular Ca2+ stores. In platelets, as in other non-excitable cells, SOCE has been reported to involve the activation of plasma membrane channels by the ER Ca2+ sensor STIM1. Despite electrophysiological studies are not possible in human platelets, indirect analyses have revealed that the Ca2+-permeable channels involve Orai1 and, most likely, TRPC1 subunits. A relevant role for the latter has not been found in mouse platelets. There is a body of evidence revealing a number of abnormalities in SOCE or in its molecular regulators that result in qualitative platelet disorders and, as a consequence, altered platelet responsiveness upon stimulation with multiple physiological agonists. Platelet SOCE abnormalities include STIM1 and Orai1 mutations. This chapter summarizes the current knowledge in this field, as well as the disorders associated to platelet SOCE dysfunction.