Relation between action potential duration and mechanical activity on rat diaphragm fibers

Effects of 3,4-diaminopyridine and tetraethylammonium
  • O. Delbono
  • B. A. Kotsias
Excitable Tissues and Central Nervous Physiology


The aim of this work was to study the electrical and mechanical properties of small bundles of rat diaphragm muscle treated with two blockers of the delayed potassium rectification channels: 3,4-diaminopyridine (3,4-DAP, 2.5 mM) and tetraethylammonium (TEA, 20 mM). Twitch tension was significantly potentiated by TEA and 3,4-DAP (39% and 59% respectively). Maximal tetanic tension was not affected by both drugs. The voltage dependence of the tension vs the resting membrane potential was shifted to lower values in TEA and 3,4-DAP. 3,4-DAP increased the caffeine contracture tension (2.5–10 mM) and lowered the caffeine contracture threshold. The duration of the action potential (measured at the level of −40 mV) was increased by TEA and 3,4-DAP solutions. This change was a consequence of the decrease in the rat of repolarization of the action potential. In addition, TEA reduced the amplitude and the rate of rise of the action potential. We suggested that the increment in the duration of the action potential and the shift of the mechanical threshold to more negative values of membrane potential might be the factors involved in the twitch potentiation induced by the TEA and 3,4-DAP solutions.

Key words

Mammalian skeletal muscle 3,4-Diaminopyridine Tetraethylammonium Potassium channels blockers Mechanical activity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bowman WC, Harvey AL, Marshall IG (1977) The actions of aminopyridines on avian muscle. Naunyn-Schmiedeberg's Arch Pharmacol 297:99–103CrossRefGoogle Scholar
  2. Caputo C (1983) Pharmacological investigations of excitation-contraction coupling. Section 10: Skeletal muscle. In: Peachey L, Adrian RA, Geiger SR (eds) Handbook of physiology, Section 10: Skeletal muscle. American Physiological Society, Bethesda, MD, USA, pp 381–414Google Scholar
  3. Delay M, Ribalet B, Vergara J (1986) Caffeine potentiation of calcium release in frog skeletal muscle fibres. J Physiol 375: 535–559CrossRefPubMedPubMedCentralGoogle Scholar
  4. Delbono O, Obejero Paz CA, Muchnik S (1985) Propiedades mecánicas del músculo esquelético en presencia de altas concentrationes de potasio y rubidio. Medicina (B. Aires) 45:327Google Scholar
  5. Dulhunty AF (1980) Potassium contractures and mechanical activation in mammalian skeletal muscles. J Membr Biol 57:223–233CrossRefPubMedGoogle Scholar
  6. Durant NN, Marshall IG (1980) The effects of 3,4-diaminopyridine on acetylcholine release at the frog neuromuscular junction. Eur J Pharmacol 67:201–208CrossRefPubMedGoogle Scholar
  7. Edman KAP, Kiessling A (1971) The time course of the active state in relation to sarcomere length and movement studied in single skeletal muscle fibers of the frog. Acta Physiol Scand 81:182CrossRefPubMedGoogle Scholar
  8. Edman KAP, Grieve DW, Nilsson E (1966) Studies of the excitation-contraction mechanism in the skeletal muscle and the myocardium. Pflügers Arch 290:320–334CrossRefGoogle Scholar
  9. Gillespie JI, Hutter OF (1975) The actions of 4-aminopyridine on the delayed potassium current in skeletal muscle fibres. J Physiol 252:70PGoogle Scholar
  10. Hagiwara S, Watanabe A (1955) The effect of tetraethylammonium chloride on the muscle membrane examined with an intracellular microelectrode. J Physiol 129:513–527CrossRefPubMedPubMedCentralGoogle Scholar
  11. Harvey AL, Marshall IG (1977) The facilitatory actions of aminopyridines and tetraethylammonium on neuromuscular transmission and muscle contractility in avian muscle. Naunyn-Schmiedeberg's Arch Pharmacol 299:53–60CrossRefGoogle Scholar
  12. Hille B (1967) The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ion. J Gen Physiol 50:1287–1302CrossRefPubMedPubMedCentralGoogle Scholar
  13. Hodgkin AL, Horowicz P (1960) Potassium contractures in single muscle fibres. J Physiol 153:386–403CrossRefPubMedPubMedCentralGoogle Scholar
  14. Hodgkin AL, Katz B (1949) The effect of sodium ions on the electrical activity of the giant axon of the squid. J Physiol 108:37–77CrossRefPubMedPubMedCentralGoogle Scholar
  15. Huang CLH (1986) The differential effects of twitch potentiators on charge movements in frog skeletal muscle. J Physiol 380:17–33CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kao CY, Stanfield PR (1970) Actions of some cations on the electrical properties and mechanical threshold of frog sartorius muscle fibers. J Gen Physiol 55:620–639CrossRefPubMedPubMedCentralGoogle Scholar
  17. Khan AR, Edman KAP (1979) Effects of 4-aminopyridine on the excitation-contraction coupling in frog and rat skeletal muscle. Acta Physiol Scand 105:443–452CrossRefPubMedGoogle Scholar
  18. Khan RA, Lemeignan M (1983) Effects of 3,4-diaminopyridine on mechanical and electrical responses of frog single muscle fibres. Acta Pharmacol Toxicol 52:181–187CrossRefGoogle Scholar
  19. Kirsch GE, Narahashi T (1978) 3,4-Diaminopyridine. A potent new potassium channel blocker. Biophys J 22:507–512CrossRefPubMedPubMedCentralGoogle Scholar
  20. Konishi M, Kurihara S, Sakai T (1985) Change in intracellular calcium ion concentration induced by caffeine and rapid cooling in frog skeletal muscle fibres. J Physiol 365:131–146CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kotsias BA, Muchnik S (1978) Reversible effect of dantrolene sodium on twitch tension of rat skeletal muscle. Arch Neurol 35:234–236CrossRefPubMedGoogle Scholar
  22. Kotsias BA, Muchnik S, Obejero Paz CA (1986). Co2+, low Ca2+, and verapamil reduce mechanical activity in rat skeletal muscles. Am J Physiol 250:C40-C46PubMedGoogle Scholar
  23. Lorković H (1971) Membrane potential and mechanical tension in white and red muscles of the rat. Am J Physiol 221:1044–1050PubMedGoogle Scholar
  24. Lüttgau HC; Kovacs L, Gottschalk G, Fuxreiter M (1983) How perchlorate improves excitation-contraction coupling in skeletal muscle fibres. Biophys J 43:247–249CrossRefPubMedPubMedCentralGoogle Scholar
  25. Mashima H, Matsumura M (1962) Roles of external ions in the excitation-contraction coupling of frog skeletal muscle. Jpn J Physiol 12:639–653CrossRefPubMedGoogle Scholar
  26. Molgó J (1978) Voltage clamp analysis of the sodium and potassium currents in skeletal muscle fibres treated with 4-aminopyridine. Experientia 34:1275–1276CrossRefPubMedGoogle Scholar
  27. Molgó J, Lundh H, Thesleff S (1980) Potency of 3,4-diaminopyridine and 4-aminopyridine on mammalian neuromuscular transmission and the effects of pH changes. Eur J Pharmacol 61:25–34CrossRefPubMedGoogle Scholar
  28. Miledi R, Parker I, Zhu PH (1984) Extracellular ions and excitation-contraction coupling in frog twitch muscle fibres. J Physiol 351:687–710CrossRefPubMedPubMedCentralGoogle Scholar
  29. Morgan KG, Bryant SH (1977) The mechanism of action of dantrolene sodium. J Pharmacol Exp Ther 201:138–147PubMedGoogle Scholar
  30. Narahashi T (1974) Chemicals as tools in the study of excitable membranes. Physiol Rev 54:813–889PubMedGoogle Scholar
  31. Savage AO (1984) Contractile effects of 4-aminopyridine on isolated frog rectus abdominis muscles. Can J Physiol Pharmacol 62:1525–1529CrossRefPubMedGoogle Scholar
  32. Schauf CL (1983) Tetramethylammonium ions alter sodium-channel gating in Myxicola. Biophys J 41:269–274CrossRefPubMedPubMedCentralGoogle Scholar
  33. Segal SS, Faulkner JA (1985) Temperature-dependent physiological stability of rat skeletal muscle in vitro. Am J Physiol 248:C265-C270PubMedGoogle Scholar
  34. Stanfield PR (1970) The differential effects of tetraethylammonium and zinc on the resting conductance of frog skeletal muscle. J Physiol 209:231–256CrossRefPubMedPubMedCentralGoogle Scholar
  35. Stefani E, Chiarandini DJ (1982) Ionic channels in skeletal muscle. Ann Rev Physiol 44:357–372CrossRefGoogle Scholar
  36. Su JY, Hasselbach W (1984) Caffeine-induced calcium release from isolated sarcoplasmic reticulum of rabbit skeletal muscle. Pflügers Arch 400:14–21CrossRefPubMedGoogle Scholar
  37. Taylor SR, Preiser H, Sandow A (1972) Action potential parameters affecting excitation-concentration coupling. J Gen Physiol 59:421–436CrossRefPubMedPubMedCentralGoogle Scholar
  38. Wendt IR, Stephenson DG (1983) Effects of caffeine on Ca-activated force production in skinned cardiac and skeletal muscle fibres of the rat. Pflügers Arch 398:210–216CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • O. Delbono
    • 1
  • B. A. Kotsias
    • 1
  1. 1.Laboratorio de NeurofisiologíaInstituto de Investigaciones Médicas “Alfredo Lanari”Buenos AiresArgentina

Personalised recommendations