Cardiovascular and Hemostatic Disorders: SOCE and Ca2+ Handling in Platelet Dysfunction

Abstract

Among the Ca entry mechanisms in platelets, store-operated Ca entry (SOCE) plays a prominent role as it is necessary to achieve full activation of platelet functions and replenish intracellular Ca stores. In platelets, as in other non-excitable cells, SOCE has been reported to involve the activation of plasma membrane channels by the ER Ca sensor STIM1. Despite electrophysiological studies are not possible in human platelets, indirect analyses have revealed that the Ca-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.

New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice

“…TRPC6 −/− mice have reduced or absent Ca 2+ entry upon stimulation with 1-oleoyl-acetyl-sn-glycerol (OAG) [201,202]. Studies have demonstrated involvement of TRPC6 in both SOCE [203] and SOCE-independent [204,205] Ca 2+ mobilisation. Although increasing evidence links TRP channel defects to cardiovascular and haemostatic pathology (reviewed in [206]), more work is required in order to understand associations with immunological or inflammatory conditions.…”

The Complex Role of Store Operated Calcium Entry Pathways and Related Proteins in the Function of Cardiac, Skeletal and Vascular Smooth Muscle Cells

“…In 1990 Kwan and colleagues demonstrated that the refilling process does not involve a direct route to the intracellular stores, but it is the result of a sequential Ca 2+ transport into the cytoplasm and the subsequent uptake from the stores by Sarco/Endoplasmic Reticulum Ca 2+ -ATPase (SERCA) (Kwan et al, 1990 ). Subsequently, SOCE has been characterized and widely studied in non-excitable cell types (Tojyo et al, 2014 ; Verkhratsky and Parpura, 2014 ; Lopez et al, 2017 ), while its role in excitable cells was difficult to demonstrate. However, few years before the first formulation of Putney's model (Putney, 1986 ), Casteels and Droogmans reported similar observations in Vascular Smooth Muscle Cells (VSMCs) (Casteels and Droogmans, 1981 ).…”

Ligustrazine suppresses platelet aggregation through inhibiting the activities of calcium sensors

“…STIM1 and Orai1 are regulated by the serum/ glucocorticoid-regulated protein kinase 1 (SGK1) (Lang, Eylenstein, Shumilina, 2012). Acting upstream of the STIM1-Orai1 pathway, SGK1 is considered a potent regulator of platelet function (Lopez, Salido, Rosado, 2017;Lang et al, 2013). Ligustrazine, which chemical name is tetramethylpyrazine (TMPZ), is an active constituent of Rhizoma ligusticum that is frequently used in traditional Chinese medicine to prevent the onset or delay the progression of cardiovascular diseases (Guo, Liu, Shi, 2016;Qian et al, 2014;Zhao, Liu, Chen, 2016).…”