INVESTIGADORES
PAFUNDO Diego Esteban
congresos y reuniones científicas
Título:
Mathematical modeling of ATP release in Goldfish hepatocytes under hypotonic shock.
Autor/es:
PAFUNDO D. E. AND CHARA O.
Lugar:
Rosario, Argentina.
Reunión:
Congreso; XXXV Reunión anual de la Sociedad Argentina de Biofísica; 2006
Resumen:
In numerous cell types hypotonic
shock induces an increase in cell volume followed by ATP release to the
extracellular space. Once in the extracellular medium, ATP can trigger
signaling pathways and also be substrate of several extracellular enzymes.
However, the release mechanism for ATP from cells remains enigmatic.
Goldfish (Carassius auratus) hepatocytes release
ATP under hypotonic shock [1]. The time course of extracellular ATP [ATP]e
is non monotonic showing a maximum at 725 ± 165 nM (106
cells)-1. The ATP releasing pathway and its particular kinetic
remain yet unclear. Its known that: 1) dead cells in hypotonic shock (up to 96.9%)
could be an [ATP]e increasing source by membrane integrity loss, 2)
Ecto-ATPase activity under experimental conditions can completely hydrolyze ATP
to adenosine [1, 2], 3) [ATP]e do not permeate into the cells but intracellular
ATP diffuses to the extracellular medium [1, 2]. In order to analyze the
contribution of the above, we developed a one dimensional mathematical model with
three compartments: the intracellular (i), an extracellular near to the cells
membrane (e1), and another one representing the bulk extracellular medium (e2).
Each compartment is described by the corresponding state variable [ATP]. In the
model, the [ATP]e is controlled by: 1) ATP contribution from dead
cells, 2) Ecto‑ATPase activity in e1, 3) ATP Diffusion from e1 to e2
compartments and 4) ATP releasing from cells by hypotonic shock. The contribution
1) is modeled loading mortality data from experimental conditions, assuming
complete ATP loosing. 2) is simulated with an hyperbolic dependence on [ATP]e,
which provided the best fit to the experimental data. 3) is emulated with a diffusion
equation. 4) is modeled with a function J describing ATP release from cells
during hypotonic shock. The model is able to explain the relative importance of
each ATP contribution showing that loss of cell viability do not explain [ATP]e,
Ecto-ATPase activity and ATP diffusion determine the non-monotonic behavior of
the time course of [ATP]e. Interestingly, the simulations show that
dJ/dt can not be zero nor a constant.