Summary
The effect of cyclic AMP on subcellular calcium turnover was studied in isolated kidney, liver and heart mitochondria. The calcium concentration of the incubating medium was determined by fluorometric methods after its separation by millipore filtration. Liver and kidney mitochondria take up calcium in exchange for H+ and lower the medium calcium to 1 to 40×10−6 m in less than 2 min. Cyclic AMP produces an instantaneous release of calcium from mitochondria and a rise in the steady-state calcium concentration of the medium. A new medium calcium level of 0.7 to 3×10−4 m is achieved in less than 3 sec and is proportional to cyclic AMP concentrations between 10−7 and 3×10−6 m. Cyclic AMP is inactive above 5×10−6 m and below 10−7 m. Cyclic IMP, 5′ AMP, dibutyryl cAMP are inactive at any concentration. Cyclic GMP is active at 10−5 m and competitively inhibits cyclic AMP action. The same staedy-state calcium level is reached from higher or, lower calcium concentrations, i.e. whether cyclic AMP is added before or after the addition of calcium to the mitochondrial suspension. At low calcium or phosphate concentrations, the calcium released by cyclic AMP is immediately reaccumulated by the mitochondria is less than 2 min with a further release of H+. This “pulse” can be repeated by sequential additions of cyclic AMP. The transient or sustained response to cyclic AMP depends on the medium calcium x phosphate product and presumably on the presence or absence of calcium phosphate precipitate inside the mitochondria. These results support the hypothesis that cyclic AMP regulates cytoplasmic calcium by controlling the mitochondrial calcium efflux rate. This mechanism may be involved in the regulation of calcium transport and in some hormonal effects mediated by cyclic AMP.
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Baker, P. F. 1972. Transport and metabolism of calcium ions in nerve.In: Progress in Biophysics and Molecular Biology. J. A. V. Butler and D. Noble, editors. Vol. 24, p. 179. Pergamon Press, New York
Borle, A. B. 1967. Membrane transfer of calcium.Clin. Orthop. 52:267
Borle, A. B. 1970. Kinetic analyses of calcium movements in cell cultures. III. Effects of calcium and parathyroid hormone in kidney cells.J. Gen. Physiol. 55:163
Borle, A. B. 1971a. Calcium transport in kidney cells and its regulation.In: Cellular Mechanisms for Calcium Transfer and Homeostasis. G. Nichols, Jr. and R. H. Wasserman, editors. p. 131. Academic Press Inc., New York
Borle, A. B. 1971b. Le turn-over du calcium dans l'organisme et les principaux points d'impact hormonaux.In: Les Hormones et le Calcium. H. P. Klotz, editor. p. 5. Expansion Scientifique Francaise, Paris
Borle, A. B. 1972a. Parathyroid hormone and cell calcium.In: Calcium, Parathyroid Hormone and the Calcitonins. R. V. Talmage and P. L. Munson, editors. p. 484. Excerpta Medica, Amsterdam
Borle, A. B. 1972b. Kinetic analysis of calcium movements in cell cultures. V. Intracellular calcium distribution in kidney cells.J. Membrane Biol. 10:45
Borle, A. B. 1973a. Calcium metabolism at the cellular level.Fed. Proc 32:1944
Borle, A. B. 1973b. Cyclic AMP regulation of calcium efflux from liver, kidney and heart mitochondria.J. Int. Res. Commun. 1:9
Borle, A. B. 1973c. Effects of cyclic AMP (cAMP) on Ca transport in mitochondria.The Physiologist 16:270
Borle, A. B., Briggs, F. N. 1968. Microdetermination, of calcium in biological material by automatic fluorometric titration.Analyt. Chem. 40:339
Godfraind, J. M., Kawamura, H., Krnjevic, K., Pumain, R. 1971. Action of dinitrophenol and some other metabolic inhibitors on cortical neurones.J. Physiol. (London) 312:199
Klein, D. C., Raisz, L. G. 1971. Role of adenine 3′,5′ monophosphate in the hormonal regulation of bone resorption: Studies with cultured fetal bone.Endocrinology 89:818
Krnjevic, K., Lisiewicz, A. 1972. Injections of calcium ions into spinal motoneurons.J. Physiol. (London) 225:363
Kuo, J. F., Greengard, P. 1969. Cyclic nucleotide-dependent kinases. IV. Widespread occurence of adenosine 3′5′-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom.Proc. Nat. Acad. Sci. 64:1349
Lehninger, A. L. 1970. Mitochondria and calcium transport.Biochem. J. 119:129
Lew, V. L. 1970. Effect of intracellular calcium on the potassium permeability of human red cells.J. Physiol. (London) 206:35P
MacManus, J. P., Perris, A. D., Whitfield, J. F., Rixon, R. H. 1970. Control of cell division in thymic lymphocytes by parathyroid hormone, thyrocalcitonin and cyclic adenosine 3′5′-monophosphate.In:Proc. Fifth Leucocyte Culture Conf. J. E. Harris, editor. p. 125. Academic Press Inc., New York
Rasmussen, H. 1970. Cell communication, calcium ion and cyclic adenosine monophosphate.Science 170:404
Rasmussen, H., Goodman, D. B. P., Tenenhouse, A. 1972. The role of cyclic AMP and calcium in cell activation.CRC Crit. Rev. Biochem. 1:95
Rixon, R. H., Whitfield, J. F., MacManus, J. P. 1970. Stimulation of mitotic activity in rat bone marrow and thymus by exogenous adenosine 3′,5′-monophosphate (cyclic AMP).Exp. Cell Res. 63:110
Romero, P. J., Whittam, R. 1971. The control by internal calcium of membrane permeability to sodium and potassium.J. Physiol. (London) 214:481
Sobel, B. E., Mayer, S. E. 1973. Brief review: Cyclic adenosine monophosphate and cardiac contractility.Circ. Res. 32:407
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Borle, A.B. Cyclic AMP stimulation of calcium efflux from kidney, liver, and heart mitochondria. J. Membrain Biol. 16, 221–236 (1974). https://doi.org/10.1007/BF01872416
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DOI: https://doi.org/10.1007/BF01872416