Electroneutral efflux of Ca2+ from liver mitochondria

Abstract

Respiring liver mitochondria were allowed to export Ca2+ on the endogenous Ca2+/nH+ antiporter in the presence of Ruthenium Red (to inhibit uptake on the Ca2+ uniporter) until a steady state was reached. Addition of sufficient of the ionophore A23187 (which catalyses Ca2+/2H+ exchange) to bring the Ca2+ and H+ gradients into equilibrium did not alter the steady state. Thermodynamic analysis showed that if a Ca2+/nH+ exchange with any value of n other than 2 was at equilibrium, addition of A23187 would have caused an easily measurable change in extramitochondrial free [Ca2+]. Therefore, the endogenous carrier of liver mitochondria catalyses electroneutral Ca2+/2H+ antiport.

The Na+‐independent Ca2+ efflux system in mitochondria is a Ca2+/2H+ exchange system

“…However, under a variety of conditions, Cyclosporin A inhibited from 5°70 to 95070 of the Na+-independent efflux and under some assay conditions the cycle of pore opening and closing appeared to be a significant and even a dominant component of the efflux. In agreement with our conclusion is the demonstration that in the presence of Ruthenium red the equilibrium distribution of Ca 2 ÷ in liver mitochondria is not altered by the ionophore A23187 (which catalyzes Ca 2 ÷/2H ÷ exchange) [16]. We have previously shown that Nigericin enhances Ca 2÷ retention in liver mitochondria even in the absence of Ruthenium red [17] and this effect too is probably due to inhibition of ApH.…”

Characteristics and possible functions of mitochondrial Ca2+ transport mechanisms

“…This mechanism appears to be nonelectrogenic [128–130]; however, no cation flux has been directly shown to be coupled to Ca 2+ efflux via this mechanism. Since [H + ] would be dominated by the H + + OH − = H 2 O equilibrium and pH buffers, and the H + flux via the transport mechanism could not be easily measured, this mechanism has been suggested by many workers to be a simple passive Ca 2+ /2H + exchanger [107, 130–133]. Nevertheless, some of the data obtained in studies of this mechanism do not fit this passive exchanger model [117, 129, 134–136].…”

“…This suggested that at least 9.5 kjoules per mole was available to this Na + -independent mechanism over and above that which would be available to a passive Ca 2+ /2H + exchanger. Since the mechanism appears to be nonelectrogenic [128–130], and there is evidence that inhibitors of electron transport also inhibit this mechanism independently of effects on ΔpH, the simplest explanation is that this mechanism is an active Ca 2+ /2H + exchanger, which obtains some energy from electron transport [17, 138]. This is consistent with earlier data obtained by Rosier et al, who carried out a partial reconstitution of this mechanism with results which suggested an active mechanism [139].…”

Anoxia-mediated calcium release through the mitochondrial permeability transition pore silences NMDA receptor currents in turtle neurons

“…, which is electroneutral and not influenced by changes in Ψ m (Brand, 1985 -efflux pathways, the most curious one being the mitochondrial permeability transition pore (mPTP).…”