Kinetic mechanisms by which nickel alters the calcium (Ca) transport in intact rat liver.

In the present work, the multiple-indicator dilution (MID) technique was used to investigate the kinetic mechanisms by which nickel (Ni) affects the calcium (Ca) transport in intact rat liver. Ca and extra- and intracellular space indicators were injected in livers perfused with 1 mM Ni, and the outflow profiles were analyzed by a mathematical model. For comparative purposes, the effects of norepinephrine were measured. The influence of Ni on the cytosolic Ca concentration ([Ca]) in human hepatoma Huh7 cells and on liver glycogen catabolism, a biological response sensitive to cellular Ca, was also evaluated. The estimated transfer coefficients of Ca transport indicated two mechanisms by which Ni increases the [Ca] in liver under steady-state conditions: (1) an increase in the net efflux of Ca from intracellular Ca stores due to a stimulus of Ca efflux to the cytosolic space along with a diminution of Ca re-entry into the cellular Ca stores; (2) a decrease in Ca efflux from the cytosolic space to vascular space, minimizing Ca loss. Glycogen catabolism activated by Ni was transient contrasting with the sustained activation induced by norepinephrine. Ni caused a partial reduction in the norepinephrine-induced stimulation in the [Ca] in Huh7 cells. Our data revealed that the kinetic parameters of Ca transport modified by Ni in intact liver are similar to those modified by norepinephrine in its first minutes of action, but the membrane receptors or Ca transporters affected by Ni seem to be distinct from those known to be modulated by norepinephrine.