title: Epithelial sodium channel modulates platelet collagen activation.
abstract: Activated platelets adhere to the exposed subendothelial extracellular matrix and undergo a rapid cytoskeletal rearrangement resulting in shape change and release of their intracellular dense and alpha granule contents to avoid hemorrhage. A central step in this process is the elevation of the intracellular Ca(2+) concentration through its release from intracellular stores and on throughout its influx from the extracellular space. The Epithelial sodium channel (ENaC) is a highly selective Na(+) channel involved in mechanosensation, nociception, fluid volume homeostasis, and control of arterial blood pressure. The present study describes the expression, distribution, and participation of ENaC in platelet migration and granule secretion using pharmacological inhibition with amiloride. Our biochemical and confocal analysis in suspended and adhered platelets suggests that ENaC is associated with Intermediate filaments (IF) and with Dystrophin-associated proteins (DAP) via α-syntrophin and β-dystroglycan. Migration assays, quantification of soluble P-selectin, and serotonin release suggest that ENaC is dispensable for migration and alpha and dense granule secretion, whereas Na(+) influx through this channel is fundamental for platelet collagen activation.
authors.affiliation: Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), Mexico City, Mexico. Electronic address: dcereced@prodigy.net.mx.
authors.forename: Doris
authors.initials: D
authors.lastname: Cerecedo
authors.affiliation: Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), Mexico City, Mexico.
authors.forename: Ivette
authors.initials: I
authors.lastname: Martínez-Vieyra
authors.affiliation: Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), Mexico City, Mexico.
authors.forename: Lea
authors.initials: L
authors.lastname: Alonso-Rangel
authors.affiliation: Laboratorio de Bioquímica, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), Mexico City, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Benítez-Cardoza
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav-IPN), Mexico City, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Ortega
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D003893:Desmin / Q000378:metabolism; D049029:Dystrophin-Associated Proteins / Q000378:metabolism; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D015539:Platelet Activation; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D003893:Desmin; D049029:Dystrophin-Associated Proteins; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; D009124:Muscle Proteins; D014746:Vimentin; C091825:syntrophin alpha1; D000584:Amiloride; D003094:Collagen; D012964:Sodium
keywords: Adhered platelets; Amiloride (AMR); Dystrophin-associated proteins (DAP); Epithelial sodium channel (ENaC); Intermediate filaments (IF); Platelet migration