INVESTIGADORES
FAILLACE Maria paula
artículos
Título:
In most animal cells, hypotonic swelling is followed by a regulatory volume decrease
Autor/es:
DIEGO E. PAFUNDO, OSVALDO CHARA, MARÍA P. FAILLACE, GERHARD KRUMSCHNABEL, PABLO J. SCHWARZBAUM
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY, INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Editorial:
AMER PHYSIOLOGICAL SOC
Referencias:
Año: 2008 vol. 294 p. 220 - 233
ISSN:
0363-6119
Resumen:
In most animal cells, hypotonic swelling is followed by a regulatory volume decrease
(RVD) thought to prevent cell death. In contrast, goldfish hepatocytes
challenged with hypotonic medium (180 mosM, HYPO) increase their
volume 1.7 times but remain swollen and viable for at least 5 h.
Incubation with ATP_S (an ATP analog) in HYPO triggers a 42%
volume decrease. This effect is concentration dependent (K1/2 _ 760
nM) and partially abolished by P2 receptor antagonists (64% inhibition).
A similar induction of RVD is observed with ATP, UTP, and
UDP, whereas adenosine inhibits RVD. Goldfish hepatocytes release
more than 500 nM ATP during the first minutes of HYPO with no
induction of RVD. The fact that similar concentrations of ATP_S did
trigger RVD could be explained by showing that ATP_S induced ATP
release. Finally, we observed that in a very small extracellular volume,
hepatocytes do show a 56% RVD. This response was diminished by
P2 receptor antagonists (73%) and increased (73%) when the extracellular
ATP hydrolysis was inhibited 72%. Using a mathematical
model, we predict that during the first 2 min of HYPO exposure the
extracellular [ATP] is mainly governed by ATP diffusion and by both
nonlytic and lytic ATP release, with almost no contribution from
ecto-ATPase activity. We show that goldfish hepatocytes under standard
HYPO (large volume) do not display RVD unless this is
triggered by the addition of micromolar concentrations of nucleotides.
However, under very low assay volumes, sufficient endogenous extracellular
[ATP] can build up to induce RVD.