Epithelial sodium channel modulates platelet collagen activation

Abstract

Activated platelets adhere to the exposed subendothelial extracellular matrix and undergo a rapidcytoskeletal rearrangement resulting in shape change and release of their intracellular dense and alphagranule contents to avoid hemorrhage. A central step in this process is the elevation of the intracellularCa2+concentration through its release from intracellular stores and on throughout its influx from theextracellular space. The Epithelial sodium channel (ENaC) is a highly selective Na+channel involved inmechanosensation, nociception, fluid volume homeostasis, and control of arterial blood pressure. Thepresent study describes the expression, distribution, and participation of ENaC in platelet migration andgranule secretion using pharmacological inhibition with amiloride. Our biochemical and confocal analy-sis in suspended and adhered platelets suggests that ENaC is associated with Intermediate filaments (IF)and with Dystrophin-associated proteins (DAP) via -syntrophin and -dystroglycan. Migration assays,quantification of soluble P-selectin, and serotonin release suggest that ENaC is dispensable for migra-tion and alpha and dense granule secretion, whereas Na+influx through this channel is fundamental forplatelet collagen activation.