The interaction of tributyltin with the mitochondrial calcium transport system of rat liver

Abstract

Tributyliin in the concentration range 0.5 to 4 μM stimulates the initial rate of Ca2+ transport by rat liver mitochondria in a simple medium consisting of 2-(N-2-hydroxyethyl-piperazine-N'-yl) ethanesulfonic acid, KCl, and succinate. The compound has no effect on Ca2+ transport in a Cl--free medium. Oligomycin, which under some conditions induces Cl- permeation, is unable to stimulate the initial rate of Ca2+ transport. Though stimulation of the initial rate of Ca2+ transport induced by tributyltin appears similar to that induced by inorganic phosphate their effects are not additive. Tributyltin also induces the release of Ca2+ from rat liver mitochondria, but the effects differ from those on the initial rate of influx in at least two ways. No inhibition of release is observed at high concentrations of tributyltin; such release also occurs in the presence of Cl--free and ion-free media. Pretreatment of mitochondria with N-ethylmaleimide to prevent Pi cycling, does not prevent the ability of tributyltin to stimulate Ca2+ influx. At all concentrations of tributyltin tested (0.1 to 2 μm) the initial rate of transport is greatly stimulated. However, while the internal Ca2+ is retained by N-ethylmaleimide-treated mitochondria in the presence of up to 0.5 μm tributyltin, addition of high concentrations of the compound (2 μm) induces a release of the Ca2+; the rate of release is slower by about 70% than that observed when Pi cycling is allowed to proceed. The implications of these findings are discussed in relation to the movement of ions across the inner mitochondrial membrane. Show more