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. 1976 Aug;57(4):565–571. doi: 10.1111/j.1476-5381.1976.tb10386.x

Effect of ionophore X-537A on desensitization rate and tension development in potassium-depolarized muscle fibres.

W A DeBassio, R L Parsons, R M Schnitzler
PMCID: PMC1667037  PMID: 1085646

Abstract

The effects of the ionophore X-537A were studied on carbamylcholine (carbachol)-induced densitization and on tension development in relaxed potassium-depolarized frog sartorius muscles. 2 X-537A accelerated carbachol-induced desensitization in Ca2+-deficient solutions without having any effect on the conductance of the membrane in the absence of carbachol or on the extent of the carbachol-induced increase in conductance. 3 In Ca2+-deficient solution, the acceleration of desensitization by the ionophore was concentration-dependent. No effect was observed with concentrations less than 5 muM and maximal acceleration was evident with 10 muM. 4 The influence of X-537A on desensitization was time-dependent. At 20 muM X-537A, there was a marked acceleration of desensitization by the end of 5 min exposure. An additional gradual acceleration occurred during a 5 to 30 min treatment. No acceleration of desensitization was evident when X-537A was simultaneously applied with carbachol to the end-plate region without prior exposure to the ionophore. 5 Desensitization also was accelerated by 30 min exposure to 20 muM X-537A in solutions containing Ca2+ or deficient in both Mg2+ and Ca2+; the rate being increased 2.8-fold in Ca2+-containing solutions, 2.9-fold in Ca2+-deficient solutions containing Mg2+, and 2.5-fold in divalent cation-deficient solutions. 6 Tension development gradually occurred in relaxed potassium-depolarized muscle preparations exposed to 20 muM X-537A. The onset of tension development occurred only after approximately 25 min of exposure both in preparations kept in Ca2+-deficient or Ca2+-containing solutions. By the end of 90 min in the ionophore, the tension developed was approximately 12% and 23% of the initial potassium contracture in those preparations maintained in the Ca2+-deficient or Ca2+-containing solutions, respectively. 7 We assume that the increase in desensitization rate following exposure to X-537A results from an elevation of the intracellular Ca2+ concentration. That muscle tension gradually increased during exposure to the ionophore supports this conclusion. The acceleration of densitization by X-537A in the absence of external Ca2+ supports the view that the site of calcium acceleration is not on the external surface of the end-plate membrane either at or near the agonist-recognition site but rather on the inner surface.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cochrane D. E., Douglas W. W., Mouri T., Nakazato Y. Calcium and stimulus-secretion coupling in the adrenal medulla: contrasting stimulating effects of the ionophores X-537A and A23187 on catecholamine output. J Physiol. 1975 Nov;252(2):363–378. doi: 10.1113/jphysiol.1975.sp011148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cochrane D. E., Parsons R. L. The interaction between caffeine and calcium in the desensitization of muscle postjunctional membrane receptors. J Gen Physiol. 1972 Apr;59(4):437–461. doi: 10.1085/jgp.59.4.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Devore D. I., Nastuk W. L. Effects of 'calcium ionophore' X537A on frog skeletal muscle. Nature. 1975 Feb 20;253(5493):644–646. doi: 10.1038/253644a0. [DOI] [PubMed] [Google Scholar]
  4. Entman M. L., Gillette P. C., Wallick E. T., Pressman B. C., Schwartz A. A study of calcium binding and uptake by isolated cardiac sarcoplasmic reticulum: the use of a new ionophore (X537A). Biochem Biophys Res Commun. 1972 Aug 21;48(4):847–853. doi: 10.1016/0006-291x(72)90685-7. [DOI] [PubMed] [Google Scholar]
  5. Godt R. E. Calcium-activated tension of skinned muscle fibers of the frog. Dependence on magnesium adenosine triphosphate concentration. J Gen Physiol. 1974 Jun;63(6):722–739. doi: 10.1085/jgp.63.6.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. HODGKIN A. L., HOROWICZ P. Potassium contractures in single muscle fibres. J Physiol. 1960 Sep;153:386–403. doi: 10.1113/jphysiol.1960.sp006541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Johnson E. W., Parsons R. L. Characteristics of postjunctional carbamylcholine receptor activation and inhibition. Am J Physiol. 1972 Mar;222(3):793–799. doi: 10.1152/ajplegacy.1972.222.3.793. [DOI] [PubMed] [Google Scholar]
  8. Kanno T., Cochrane D. E., Douglas W. W. Exocytosis (secretory granule extrusion) induced by injection of calcium into mast cells. Can J Physiol Pharmacol. 1973 Dec;51(12):1001–1004. doi: 10.1139/y73-153. [DOI] [PubMed] [Google Scholar]
  9. Lambert D. H., Parsons R. L. Influence of polyvalent cations on the activation of muscle end plate receptors. J Gen Physiol. 1970 Sep;56(3):309–321. doi: 10.1085/jgp.56.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lapa A. J., Albuquerque E. X., Daly J. An electrophysiological study of the effects of D-tubocurarine, atropine, and alpha-bungarotoxin on the cholinergic receptor in innervated and chronically denervated mammalian skeletal muscles. Exp Neurol. 1974 May;43(2):375–398. doi: 10.1016/0014-4886(74)90179-4. [DOI] [PubMed] [Google Scholar]
  11. Levy J. V., Cohen J. A., Inesi G. Contractile effects of a calcium ionophore. Nature. 1973 Apr 13;242(5398):461–463. doi: 10.1038/242461a0. [DOI] [PubMed] [Google Scholar]
  12. Lin D. C., Kun E. Mode of action of the antibiotic X-537A on mitochondrial glutamate oxidation. Biochem Biophys Res Commun. 1973 Feb 5;50(3):820–825. doi: 10.1016/0006-291x(73)91318-1. [DOI] [PubMed] [Google Scholar]
  13. Magazanik L. G., Vyskocil F. Dependence of acetylcholine desensitization on the membrane potential of frog muscle fibre and on the ionic changes in the medium. J Physiol. 1970 Oct;210(3):507–518. doi: 10.1113/jphysiol.1970.sp009223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Manthey A. A. Further studies of the effect of calcium on the time course of action of carbamylcholine at the neuromuscular junction. J Gen Physiol. 1970 Sep;56(3):407–419. doi: 10.1085/jgp.56.3.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Manthey A. A. The antagonistic effects of calcium and potassium on the time course of action of carbamylcholine at the neuromuscular junction. J Membr Biol. 1972;9(4):319–340. [PubMed] [Google Scholar]
  16. Manthey A. A. The effect of calcium on the desensitization of membrane receptors at the neuromuscular junction. J Gen Physiol. 1966 May;49(5):963–976. doi: 10.1085/jgp.49.5.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miledi R. Transmitter release induced by injection of calcium ions into nerve terminals. Proc R Soc Lond B Biol Sci. 1973 Jul 3;183(1073):421–425. doi: 10.1098/rspb.1973.0026. [DOI] [PubMed] [Google Scholar]
  18. Nastuk W. L., Parsons R. L. Factors in the inactivation of postjunctional membrane receptors of frog skeletal muscle. J Gen Physiol. 1970 Aug;56(2):218–249. doi: 10.1085/jgp.56.2.218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Parsons R. L., Johnson E. W., Lambert D. H. Effects of lanthanum and calcium on chronically denervated muscle fibers. Am J Physiol. 1971 Feb;220(2):401–405. doi: 10.1152/ajplegacy.1971.220.2.401. [DOI] [PubMed] [Google Scholar]
  20. Parsons R. L., Schnitzler R. M., Cochrane D. E. Inhibition of end-plate desensitization by sodium. Am J Physiol. 1974 Jul;227(1):96–100. doi: 10.1152/ajplegacy.1974.227.1.96. [DOI] [PubMed] [Google Scholar]
  21. Pressman B. C. Properties of ionophores with broad range cation selectivity. Fed Proc. 1973 Jun;32(6):1698–1703. [PubMed] [Google Scholar]
  22. Scarpa A., Baldassare J., Inesi G. The effect of calcium ionophores on fragmented sarcoplasmic reticulum. J Gen Physiol. 1972 Dec;60(6):735–749. doi: 10.1085/jgp.60.6.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. THESLEFT S. The mode of neuromuscular block caused by acetylcholine, nicotine, decamethonium and succinylcholine. Acta Physiol Scand. 1955 Oct 27;34(2-3):218–231. doi: 10.1111/j.1748-1716.1955.tb01242.x. [DOI] [PubMed] [Google Scholar]

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