Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Feb;77(2):638–640. doi: 10.1172/JCI112348

Effect of theophylline on membrane potential and contractile force in hamster diaphragm muscle in vitro.

S Esau
PMCID: PMC423404  PMID: 3944272

Abstract

Theophylline enhances the force of diaphragmatic contraction and delays fatigue. The mechanism is not known, but recent evidence suggests it may act at the cell membrane. To test this hypothesis, we studied the effect of theophylline on resting membrane potential and tension in hamster diaphragm cells. Muscle strips were obtained from five adult hamsters and placed in Krebs solution, aerated with 95% O2, 5% CO2. Resting membrane potential was measured using 3-M KCl-filled glass microelectrodes; 15-22 fibers in each strip were sampled. Force frequency curves (twitch to 100 Hz) were obtained. The muscle bath was then changed to one containing 100 mg/liter (0.55) theophylline. Resting membrane potential was -76 +/- 3 mV (mean +/- S.D.) in Krebs solution and increased to -85 +/- 3 mV (P less than 0.01) with added theophylline. Tension increased from 5% (at 100 Hz) to 20% (at 10 Hz) with theophylline. Hyperpolarization indicates an increase in intracellular to extracellular potassium concentration. Net potassium outflow occurs with each contraction, causing the cell membrane to become depolarized with repeated contractions, ultimately leading to fatigue. The hyperpolarization of the skeletal muscle cell membrane observed with theophylline may play an important role in prolonging time to fatigue.

Full text

PDF
638

Selected References

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

  1. Aubier M., De Troyer A., Sampson M., Macklem P. T., Roussos C. Aminophylline improves diaphragmatic contractility. N Engl J Med. 1981 Jul 30;305(5):249–252. doi: 10.1056/NEJM198107303050503. [DOI] [PubMed] [Google Scholar]
  2. Aubier M., Murciano D., Viires N., Lecocguic Y., Pariente R. Diaphragmatic contractility enhanced by aminophylline: role of extracellular calcium. J Appl Physiol Respir Environ Exerc Physiol. 1983 Feb;54(2):460–464. doi: 10.1152/jappl.1983.54.2.460. [DOI] [PubMed] [Google Scholar]
  3. Buckley B. M., Braithwaite R. A., Vale J. A. Theophylline poisoning. Lancet. 1983 Sep 10;2(8350):618–618. doi: 10.1016/s0140-6736(83)90695-5. [DOI] [PubMed] [Google Scholar]
  4. Busis N. A., Weight F. F. Spike after-hyperpolarisation of a sympathetic neurone is calcium sensitive and is potentiated by theophylline. Nature. 1976 Sep 30;263(5576):434–436. doi: 10.1038/263434a0. [DOI] [PubMed] [Google Scholar]
  5. Hall K. W., Dobson K. E., Dalton J. G., Ghignone M. C., Penner S. B. Metabolic abnormalities associated with intentional theophylline overdose. Ann Intern Med. 1984 Oct;101(4):457–462. doi: 10.7326/0003-4819-101-4-457. [DOI] [PubMed] [Google Scholar]
  6. Hirche H., Schumacher E., Hagemann H. Extracellular K+ concentration and K+ balance of the gastrocnemius muscle of the dog during exercise. Pflugers Arch. 1980 Sep;387(3):231–237. doi: 10.1007/BF00580975. [DOI] [PubMed] [Google Scholar]
  7. Hník P., Holas M., Krekule I., Kŭriz N., Mejsnar J., Smiesko V., Ujec E., Vyskocil F. Work-induced potassium changes in skeletal muscle and effluent venous blood assessed by liquid ion-exchanger microelectrodes. Pflugers Arch. 1976 Mar 11;362(1):85–94. doi: 10.1007/BF00588685. [DOI] [PubMed] [Google Scholar]
  8. Jones D. A., Howell S., Roussos C., Edwards R. H. Low-frequency fatigue in isolated skeletal muscles and the effects of methylxanthines. Clin Sci (Lond) 1982 Aug;63(2):161–167. doi: 10.1042/cs0630161. [DOI] [PubMed] [Google Scholar]
  9. Kentera D., Varagić V. M. The effects of cyclic N-2-O-dibutyryl- adenosine 3',5'-monophosphate, adrenaline and aminophylline on the isometric contractility of the isolated hemidiaphragm of the rat. Br J Pharmacol. 1975 Jul;54(3):375–381. doi: 10.1111/j.1476-5381.1975.tb07578.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kerr L. M., Sperelakis N. Ca2+-dependent slow action potentials in normal and dystrophic mouse skeletal muscle. Am J Physiol. 1983 Nov;245(5 Pt 1):C415–C422. doi: 10.1152/ajpcell.1983.245.5.C415. [DOI] [PubMed] [Google Scholar]
  11. Knochel J. P., Blachley J. D., Johnson J. H., Carter N. W. Muscle cell electrical hyperpolarization and reduced exercise hyperkalemia in physically conditioned dogs. J Clin Invest. 1985 Feb;75(2):740–745. doi: 10.1172/JCI111755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Latorre R., Vergara C., Hidalgo C. Reconstitution in planar lipid bilayers of a Ca2+-dependent K+ channel from transverse tubule membranes isolated from rabbit skeletal muscle. Proc Natl Acad Sci U S A. 1982 Feb;79(3):805–809. doi: 10.1073/pnas.79.3.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Murciano D., Aubier M., Lecocguic Y., Pariente R. Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease. N Engl J Med. 1984 Aug 9;311(6):349–353. doi: 10.1056/NEJM198408093110601. [DOI] [PubMed] [Google Scholar]
  14. Sigrist S., Thomas D., Howell S., Roussos C. The effect of aminophylline on inspiratory muscle contractility. Am Rev Respir Dis. 1982 Jul;126(1):46–50. doi: 10.1164/arrd.1982.126.1.46. [DOI] [PubMed] [Google Scholar]
  15. Supinski G. S., Deal E. C., Jr, Kelsen S. G. The effects of caffeine and theophylline on diaphragm contractility. Am Rev Respir Dis. 1984 Sep;130(3):429–433. doi: 10.1164/arrd.1984.130.3.429. [DOI] [PubMed] [Google Scholar]
  16. Varagić V. M., Kentera D. Interactions of calcium, dibutyryl cyclic AMP, isoprenaline and aminophylline on the isometric contraction of the isolated hemidiaphragm of the rat. Naunyn Schmiedebergs Arch Pharmacol. 1978 May;303(1):47–53. doi: 10.1007/BF00496184. [DOI] [PubMed] [Google Scholar]
  17. Weber A. The mechanism of the action of caffeine on sarcoplasmic reticulum. J Gen Physiol. 1968 Nov;52(5):760–772. doi: 10.1085/jgp.52.5.760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zierler K. L. Possible mechanisms of insulin action on membrane potential and ion fluxes. Am J Med. 1966 May;40(5):735–739. doi: 10.1016/0002-9343(66)90154-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES