Abstract
X-537 A and A 23187, two antibiotics which form liphophilic complexes with divalent cations, function as ionophores in vesicular fragments of sarcoplasmic reticulum (SR). Addition of either ionophore to SR preloaded with calcium in the presence of adenosine triphosphate (ATP), causes rapid release of calcium. Furthermore, net calcium accumulation by SR is prevented, when the ionophores are added to the reaction mixture before ATP. On the contrary, ATP-independent calcium binding to SR is not inhibited. This effect is specific for the two antibiotics and could not be reproduced, either by inactive derivatives, or by other known ionophores. Neither ionophore produces alterations of the electron microscopic appearance of SR membranes or inhibition of the calcium-dependent ATPase. In fact, the burst of ATP hydrolysis obtained on addition of calcium, is prolonged in the presence of the ionophores. Lanthanum inhibits ATP-independent calcium binding to SR, ATP-dependent calcium accumulation and calcium-dependent ATPase. However, addition of lanthanum to SR preloaded in the presence of ATP, does not cause calcium release. The reported experiments indicated that: (a) ATP-dependent calcium accumulation by SR results in primary formation of calcium ion gradients across the membrane. (b) Most of the accumulated calcium is not available for displacement by lanthanum on the outer surface of the membrane. (c) Calcium ionophores induce rapid equilibration of the gradients, by facilitating cation diffusion across the membrane.
Full Text
The Full Text of this article is available as a PDF (876.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Chance B. Principles of differential spectrophotometry with special reference to the dual wavelength method. Methods Enzymol. 1972;24:322–335. doi: 10.1016/0076-6879(72)24080-0. [DOI] [PubMed] [Google Scholar]
- Chevallier J., Butow R. A. Calcium binding to the sarcoplasmic reticulum of rabbit skeletal muscle. Biochemistry. 1971 Jul 6;10(14):2733–2737. doi: 10.1021/bi00790a012. [DOI] [PubMed] [Google Scholar]
- Hagiwara S., Takahashi K. Surface density of calcium ions and calcium spikes in the barnacle muscle fiber membrane. J Gen Physiol. 1967 Jan;50(3):583–601. doi: 10.1085/jgp.50.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henderson P. J., McGivan J. D., Chappell J. B. The action of certain antibiotics on mitochondrial, erythrocyte and artificial phospholipid membranes. The role of induced proton permeability. Biochem J. 1969 Feb;111(4):521–535. doi: 10.1042/bj1110521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inesi G. Active transport of calcium ion in sarcoplasmic membranes. Annu Rev Biophys Bioeng. 1972;1:191–210. doi: 10.1146/annurev.bb.01.060172.001203. [DOI] [PubMed] [Google Scholar]
- Inesi G., Almendares J. Interaction of fragmented sarcoplasmic reticulum with 14C-ADP, 14C-ATP, and 32P-ATP. Effect of Ca and Mg. Arch Biochem Biophys. 1968 Aug;126(2):733–735. doi: 10.1016/0003-9861(68)90464-5. [DOI] [PubMed] [Google Scholar]
- Inesi G., Asai H. Trypsin digestion of fragmented sarcoplasmic reticulum. Arch Biochem Biophys. 1968 Aug;126(2):469–477. doi: 10.1016/0003-9861(68)90431-1. [DOI] [PubMed] [Google Scholar]
- Inesi G., Goodman J. J., Watanabe S. Effect of diethyl ether on the adenosine triphosphatase activity and the calcium uptake of fragmented sarcoplasmic reticulum of rabbit skeletal muscle. J Biol Chem. 1967 Oct 25;242(20):4637–4643. [PubMed] [Google Scholar]
- Inesi G., Scarpa A. [Fast kinetics of adenosine triphosphate dependent Ca 2+ uptake by fragmented sarcoplasmic reticulum]. Biochemistry. 1972 Feb 1;11(3):356–359. doi: 10.1021/bi00753a008. [DOI] [PubMed] [Google Scholar]
- Kinsky S. C. Antibiotic interaction with model membranes. Annu Rev Pharmacol. 1970;10:119–142. doi: 10.1146/annurev.pa.10.040170.001003. [DOI] [PubMed] [Google Scholar]
- LETTVIN J. Y., PICKARD W. F., MCCULLOCH W. S., PITTS W. A THEORY OF PASSIVE ION FLUX THROUGH AXON MEMBRANES. Nature. 1964 Jun 27;202:1338–1339. doi: 10.1038/2021338a0. [DOI] [PubMed] [Google Scholar]
- Lardy H. A., Graven S. N., Estrada S. Specific induction and inhibition of cation and anion transport in mitochondria. Fed Proc. 1967 Sep;26(5):1355–1360. [PubMed] [Google Scholar]
- McFarland B. H., Inesi G. Solubilization of sarcoplasmic reticulum with Triton X-100. Arch Biochem Biophys. 1971 Aug;145(2):456–464. doi: 10.1016/s0003-9861(71)80005-x. [DOI] [PubMed] [Google Scholar]
- Mela L., Chance B. Calcium carrier and the "high affinity calcium binding site" in mitochondria. Biochem Biophys Res Commun. 1969 May 22;35(4):556–559. doi: 10.1016/0006-291x(69)90383-0. [DOI] [PubMed] [Google Scholar]
- OHNISHI T., EBASHI S. THE VELOCITY OF CALCIUM BINDING OF ISOLATED SARCOPLASMIC RETICULUM. J Biochem. 1964 Jun;55:599–603. doi: 10.1093/oxfordjournals.jbchem.a127932. [DOI] [PubMed] [Google Scholar]
- Pressman B. C., Harris E. J., Jagger W. S., Johnson J. H. Antibiotic-mediated transport of alkali ions across lipid barriers. Proc Natl Acad Sci U S A. 1967 Nov;58(5):1949–1956. doi: 10.1073/pnas.58.5.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pressman B. C. Ionophorous antibiotics as models for biological transport. Fed Proc. 1968 Nov-Dec;27(6):1283–1288. [PubMed] [Google Scholar]
- Scarpa A., Azzone G. F. The mechanism of ion translocation in mitochondria. 4. Coupling of K+ efflux with Ca2+ uptake. Eur J Biochem. 1970 Feb;12(2):328–335. doi: 10.1111/j.1432-1033.1970.tb00854.x. [DOI] [PubMed] [Google Scholar]
- Scarpa A., Inesi G. Ionophore mediated equilibration of calcium ion gradients in fragmented-sarcoplasmic reticulum. FEBS Lett. 1972 May 15;22(3):273–276. doi: 10.1016/0014-5793(72)80248-5. [DOI] [PubMed] [Google Scholar]
- Scarpa A. Spectrophotometric measurement of calcium by murexide. Methods Enzymol. 1972;24:343–351. doi: 10.1016/0076-6879(72)24082-4. [DOI] [PubMed] [Google Scholar]
- Weber A. Regulatory mechanisms of the calcium transport system of fragmented rabbit sarcoplasmic rticulum. I. The effect of accumulated calcium on transport and adenosine triphosphate hydrolysis. J Gen Physiol. 1971 Jan;57(1):50–63. doi: 10.1085/jgp.57.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Breemen C., De Weer P. Lanthanum inhibition of 45Ca efflux from the squid giant axon. Nature. 1970 May 23;226(5247):760–761. doi: 10.1038/226760a0. [DOI] [PubMed] [Google Scholar]