Dynamic regulation of cell volume and extracellular ATP of human erythrocytes

Introduction: The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect cell volume (Vr), we explored the dynamic regul...

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Autores principales: Leal Denis, M. Florencia, Álvarez, Hugo Ariel, Lauri, Natalia, Alvarez, Cora L., Chara, Osvaldo, Schwarzbaum, Pablo J.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2016
Materias:
Química
Pyridones
Ribonucleosides
Endothelial cells
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85726
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-85726
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
Pyridones
Ribonucleosides
Endothelial cells
spellingShingle Química
Pyridones
Ribonucleosides
Endothelial cells
Leal Denis, M. Florencia
Álvarez, Hugo Ariel
Lauri, Natalia
Alvarez, Cora L.
Chara, Osvaldo
Schwarzbaum, Pablo J.
Dynamic regulation of cell volume and extracellular ATP of human erythrocytes
topic_facet Química
Pyridones
Ribonucleosides
Endothelial cells
description Introduction: The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect cell volume (Vr), we explored the dynamic regulation between Vr and ATPe. Methods and Treatments: We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors. Results: In rbcs 10 μM MST7 promoted acute, strongly correlated changes in [ATPe] and Vr. Whereas MST7 induced increases of 10% in Vr and 190 nM in [ATPe], blocking swelling in a hyperosmotic medium + MST7 reduced [ATPe] by 40%. Pre-incubation of rbcs with 10 μM of either carbenoxolone or probenecid, two inhibitors of the ATP conduit pannexin 1, reduced [ATPe] by 40-50% and swelling by 40-60%, while in the presence of 80 U/mL apyrase, an ATPe scavenger, cell swelling was prevented. While exposure to 10 μM NF110, a blocker of ATP-P2X receptors mediating sodium influx, reduced [ATPe] by 48%, and swelling by 80%, incubation of cells in sodium free medium reduced swelling by 92%. Analysis and Discussion: Results were analyzed by means of a mathematical model where ATPe kinetics and Vr kinetics were mutually regulated. Model dependent fit to experimental data showed that, upon MST7 exposure, ATP efflux required a fast 1960-fold increase of ATP permeability, mediated by two kinetically different conduits, both of which were activated by swelling and inactivated by time. Both experimental and theoretical results suggest that, following MST7 exposure, ATP is released via two conduits, one of which is mediated by pannexin 1. The accumulated ATPe activates P2X receptors, followed by sodium influx, resulting in cell swelling, which in turn further activates ATP release. Thus swelling and P2X receptors constitute essential components of a positive feedback loop underlying ATP-induced ATP release of rbcs.
format Articulo
Articulo
author Leal Denis, M. Florencia
Álvarez, Hugo Ariel
Lauri, Natalia
Alvarez, Cora L.
Chara, Osvaldo
Schwarzbaum, Pablo J.
author_facet Leal Denis, M. Florencia
Álvarez, Hugo Ariel
Lauri, Natalia
Alvarez, Cora L.
Chara, Osvaldo
Schwarzbaum, Pablo J.
author_sort Leal Denis, M. Florencia
title Dynamic regulation of cell volume and extracellular ATP of human erythrocytes
title_short Dynamic regulation of cell volume and extracellular ATP of human erythrocytes
title_full Dynamic regulation of cell volume and extracellular ATP of human erythrocytes
title_fullStr Dynamic regulation of cell volume and extracellular ATP of human erythrocytes
title_full_unstemmed Dynamic regulation of cell volume and extracellular ATP of human erythrocytes
title_sort dynamic regulation of cell volume and extracellular atp of human erythrocytes
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/85726
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