Open AccessRegulation of Ca 2+ Efflux in Rat Liver Mitochondria
Author(s) -
BERNARDI Paolo,
AZZONE Giovanni Felice
Publication year - 1983
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1983.tb07578.x
Subject(s) - efflux , ruthenium red , chemistry , valinomycin , membrane potential , biophysics , delta , mitochondrion , steady state (chemistry) , cytosol , calcium , biochemistry , biology , enzyme , organic chemistry , engineering , aerospace engineering
1 The paper analyzes the relationship between membrane potential ( ΔΨ ), steady state pCa 0 (‐log [Ca 2+ ] in the outer aqueous phase) and rate of ruthenium‐red‐induced Ca 2+ efflux in liver mitochondria. Energized liver mitochondria maintain a pCa 0 of about 6.0 in the presence of 1.5 mM Mg 2+ and 0.5 mM P i . A slight depression of ΔΨ results in net Ca 2+ uptake leading to an increased steady state pCa 0 . On the other hand, a more marked depression of ΔΨ results in net Ca 2+ efflux, leading to a decreased steady‐state pCa 0 . These results reflect a biphasic relationship between ΔΨ and pCa 0 , in that pCa 0 increases of ΔΨ up to a value of about 130 mV, whereas a further increase of ΔΨ above 130 mV results in a decrease of pCa 0 . The phenomenon of Ca 2+ uptake following a depression of ΔΨ is independent of the tool used to affect ΔΨ whether by inward K + current via valinomycin, or by inward H + current current through protonophores or through, F 1 ‐ATP synthase, or by restriction of e − flow. 2 The pathway for Ca 2+ efflux is considerably activated by stretching of the inner membrane in hypotonic media. This activation is accompanied by a decreased pCa 0 at steady state and by an increased rate of ruthenium‐red‐induced Ca 2+ efflux. By restricting the rate of e − flow in hypotonically treated mitochondria, a marked dependence of the rate of ruthenium‐red‐induced Ca 2+ efflux on the value of ΔΨ is observed, in that the rate of Ca 2+ efflux increases with the value of ΔΨ . The pCa 0 is linearly related to the rate of Ca 2+ efflux. 3 Activation of oxidative phosphorylation via addition of hexokinase + glucose to ATP‐supplemented mitochondria, is followed by a phase of Ca 2+ uptake, which is reversed by atractyloside. 4 These findings support the view that Ca 2+ efflux in steady state mitochondria occurs through an independent, ΔΨ ‐controlled pathway and that changes of ΔΨ during oxidative phosphorylation can effectively modulate mitochondrial Ca 2+ distribution by inhibiting or activating the ΔΨ ‐controlled Ca 2+ efflux pathway.