Calcium mitochondrial efflux

While our data using this technique are still preliminary, we have observed that 25 yU/ml insulin inhibits the rate of calcium efflux from renal slices (28). This effect of insulin was gradually reduced at the higher concentrations of insulin. The effects of insulin on calcium exchange appear to be localized in the mitochondrial compartment. Further work is needed to determine whether insulin affects specific enzyme systems which are known to play a role in renal calcium transport, and which cellular or subcellular compartments are involved. This would substantially increase our understanding of the regulation of urinary calcium excretion, and of ways in which excessive loss of calcium by this route might be avoided. 

Akerman, K.E., 1978, Changes in membrane potential during calcium ion influx and efflux across the mitochondrial membrane, Biochim. Biophys. Acta 502, pp. 359-366... 

Crompton, M., Capano, M., and Carafoli, E., 1976, The sodium-induced efflux of calcium from heart mitochondria. A possible mechanism for the regulation of mitochondrial calcium, Eur. J. Biochem. 

Wasaki, S., Sakaida, I., Uchida, K., Kimura, T., Kayano, K., and Okita, K., 1997, Preventive effect of cyclosporin A on experimentally induced acute liver injury in rats, Liver 17, pp. 107-114 Weiss, J.N., Korge, P., Honda, H. M., and Ping, P., 2003, Role of the mitochondrial permeability transition in myocardial disease, Circ. Res 93, pp. 292-301 Wingrove, D.E. and Gunter, T. E., 1986a, Kinetics of mitochondrial calcium transport. I. Characteristics of the sodium-independent calcium efflux mechanism of liver mitochondria, J. Biol. Chem. 261, pp.15159-15165... 

P2. Packer, M. A., and Murphy, M. P., Peroxynitrite formed by simultaneous nitric oxide and superoxide generation causes cyclosporin-A-sensitive mitochondrial calcium efflux and depolarisation. Eur. J. Biochem. 234, 231—239 (1995). 

The inner mitochondrial membrane may function primarily as a calcium sink, taking up excess calcium in the cytosol that results from hormonal activation of the cell. At cytosolic Ca + concentrations greater than 0.6 /rmol/L, the mitochondrial calcium pump is activated and stores calcium in the mitochondrial matrix as a nonionic, rapidly exchangeable, phosphate salt. At low cytosolic calcium concentrations, the inner mitochondrial membrane allows Ca + to leak into the cytosol. The capacity of the active influx pathway (the pump) is much greater than that of the passive efflux route (the leak). The mitochondrial pump-leak system may serve to fine-tune the cytosolic calcium concentration while the plasma membrane is the principal safeguard against entry of toxic amounts of calcium into the cell. 

Mitochondrial dysfunction is believed to play a vital role in the pathogenesis of acute renal failure. In the face of inadequate production of mitochondrial ATP, sodium and calcium efflux from the cell, which requires ATP, is curtailed. This leads to the swelling of the cell and activation of the calcium-calmodulin complex. The latter may activate phospholipases, which in turn can damage the cell membrane and cause swelling of the cell, leading to its death. The cell debris serves as a substrate for tubular obstruction and supports the maintenance phase of acute renal failure. Complications of casts solidifying in the tubular lumen can be avoided by early measures to prevent cell death. 

Studies of calcium movement under the influence of serotonin and cAMP revealed that serotonin stimulates both calcium uptake and calcium loss from the secretory cell. cAMP does also stimulate calcium efflux. In addition to stimulating secretion, cAMP is also believed to increase the levels of calcium of the cytosol by releasing calcium from the mitochondrial stores and to modulate the permeability of the cell membrane to chloride ions. 

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