Cardiovascular system SOCE and Ca2+ handling in platelet dysfunction

Abstract

Store-operated Ca2+ entry (SOCE) is a major mechanism for Ca2+ influx in platelets, where Ca2+ influx through plasma membrane channels is necessary to achieve full activation of platelet functions. In these cell fragments, SOCE has been reported to involve the dynamic association of the ER Ca2+ sensor STIM1 and different plasma membrane Ca2+ permeable channels, including Orai1 and several TRPC members. A number of intracellular elements have been shown to participate in the regulation of SOCE in platelets, including the cytoskeleton or proteins of the SNARE family. Recent studies have revealed a number of abnormalities in SOCE or in its molecular regulators that result in qualitative platelet disorders and, as a consequence, in a reduced or absent platelet responsiveness upon stimulation with multiple physiological agonists. Platelet SOCE abnormalities include ion channel mutations or altered expression, as well as dysfunction of cytoskeleton-associated proteins. This chapter summarizes the recent advances in this field, as well as the disorders associated to platelet SOCE dysfunction.