Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1980;300:269–282. doi: 10.1113/jphysiol.1980.sp013161

The intracellular sodium activity of sheep heart Purkinje fibres: effects of local anaesthetics and tetrodotoxin

Joachim W Deitmer 1,*, David Ellis 1,†
PMCID: PMC1279354  PMID: 7381786

Abstract

1. The intracellular Na activity (aNai) of quiescent sheep heart Purkinje fibres has been measured using Na+-sensitive glass micro-electrodes. The effects of local anaesthetics (procaine and lidocaine) and tetrodotoxin (TTX) have been investigated.

2. Local anaesthetics reduced the steady-state level of the intracellular Na activity in a dose-dependent manner. The highest concentrations used (10-2 M) reduced the intracellular Na activity by about 25%.

3. TTX decreased the steady-state level of the intracellular Na activity. At a concentration of 10-6 g/ml. (3·13 × 10-6 M), TTX produced a decrease in intracellular Na activity of approximately 10%.

4. The initial rate of rise of the intracellular Na activity upon addition of the cardioactive steroid strophanthidin (10-5 M) was used to estimate the net passive Na influx.

5. Procaine (5 × 10-4 M) caused a 50% reduction of this rate of rise of the intracellular Na activity. The highest concentration of procaine used (10-2 M) decreased the rate of rise by approximately 80%.

6. Procaine (5 × 10-3 M) also reduced the rate of rise of intracellular Na produced by the removal of external K (Ko), and prevented the large depolarization associated with the absence of Ko.

7. TTX also produced a decrease in the rate of rise of the intracellular Na activity that occurs upon addition of strophanthidin. A maximum effect was produced in our experiments at a TTX concentration of 10-6 g/ml. At this concentration the rate of rise of intracellular Na activity was reduced by approximately 40% at a membrane potential of -70 mV.

8. We conclude from our experiments that the effects of local anaesthetics and TTX on the intracellular Na activity are brought about by a reduction of the Na permeability of the cell membrane, and that at the normal resting potential, Na entry through TTX-sensitive channels contributes greatly to the total net Na influx.

Full text

PDF
269

Selected References

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

  1. Arnsdorf M. F., Bigger J. T., Jr Effect of lidocaine hydrochloride on membrane conductance in mammalian cardiac Purkinje fibers. J Clin Invest. 1972 Sep;51(9):2252–2263. doi: 10.1172/JCI107034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baer M., Best P. M., Reuter H. Voltage-dependent action of tetrodotoxin in mammalian cardiac muscle. Nature. 1976 Sep 23;263(5575):344–345. doi: 10.1038/263344a0. [DOI] [PubMed] [Google Scholar]
  3. Baker P. F., Blaustein M. P., Keynes R. D., Manil J., Shaw T. I., Steinhardt R. A. The ouabain-sensitive fluxes of sodium and potassium in squid giant axons. J Physiol. 1969 Feb;200(2):459–496. doi: 10.1113/jphysiol.1969.sp008703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bigger J. T., Jr, Mandel W. J. Effect of lidocaine on conduction in canine Purkinje fibers and at the ventricular muscle-Purkinje fiber junction. J Pharmacol Exp Ther. 1970 Apr;172(2):239–254. [PubMed] [Google Scholar]
  5. Blankenship J. E. Tetrodotoxin: from poison to powerful tool. Perspect Biol Med. 1976 Summer;19(4):509–526. doi: 10.1353/pbm.1976.0071. [DOI] [PubMed] [Google Scholar]
  6. CARMELIET E. E. Chloride ions and the membrane potential of Purkinje fibres. J Physiol. 1961 Apr;156:375–388. doi: 10.1113/jphysiol.1961.sp006682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen I. S., Strichartz G. R. On the voltage-dependent action of tetrodotoxin. Biophys J. 1977 Mar;17(3):275–279. doi: 10.1016/S0006-3495(77)85656-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis L. D., Temte J. V. Electrophysiological actions of lidocaine on canine ventricular muscle and Purkinje fibers. Circ Res. 1969 May;24(5):639–655. doi: 10.1161/01.res.24.5.639. [DOI] [PubMed] [Google Scholar]
  9. Deitmer J. W., Ellis D. Changes in the intracellular sodium activity of sheep heart Purkinje fibres produced by calcium and other divalent cations. J Physiol. 1978 Apr;277:437–453. doi: 10.1113/jphysiol.1978.sp012283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Deitmer J. W., Ellis D. The intracellular sodium activity of cardiac Purkinje fibres during inhibition and re-activation of the Na-K pump. J Physiol. 1978 Nov;284:241–259. doi: 10.1113/jphysiol.1978.sp012539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dudel J., Peper K., Rüdel R., Trautwein W. The effect of tetrodotoxin on the membrane current in cardiac muscle (Purkinje fibers). Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;295(3):213–226. doi: 10.1007/BF01844101. [DOI] [PubMed] [Google Scholar]
  12. Eckert R., Lux H. D. A voltage-sensitive persistent calcium conductance in neuronal somata of Helix. J Physiol. 1976 Jan;254(1):129–151. doi: 10.1113/jphysiol.1976.sp011225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ellis D. The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres. J Physiol. 1977 Dec;273(1):211–240. doi: 10.1113/jphysiol.1977.sp012090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Frieden J. Antiarrhythmic drugs. VII. Lidocaine as an antiarrhythmic agent. Am Heart J. 1965 Nov;70(5):713–715. doi: 10.1016/0002-8703(65)90399-6. [DOI] [PubMed] [Google Scholar]
  15. Gadsby D. C., Cranefield P. F. Two levels of resting potential in cardiac Purkinje fibers. J Gen Physiol. 1977 Dec;70(6):725–746. doi: 10.1085/jgp.70.6.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gianelly R., von der Groeben J. O., Spivack A. P., Harrison D. C. Effect of lidocaine on ventricular arrhythmias in patients with coronary heart disease. N Engl J Med. 1967 Dec 7;277(23):1215–1219. doi: 10.1056/NEJM196712072772301. [DOI] [PubMed] [Google Scholar]
  17. Gliklich J. I., Hoffman B. F. Sites of action and active forms of lidocaine and some derivatives on cardiac Purkinje fibers. Circ Res. 1978 Oct;43(4):638–651. doi: 10.1161/01.res.43.4.638. [DOI] [PubMed] [Google Scholar]
  18. HODGKIN A. L., HUXLEY A. F. The dual effect of membrane potential on sodium conductance in the giant axon of Loligo. J Physiol. 1952 Apr;116(4):497–506. doi: 10.1113/jphysiol.1952.sp004719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hille B. Potassium channels in myelinated nerve. Selective permeability to small cations. J Gen Physiol. 1973 Jun;61(6):669–686. doi: 10.1085/jgp.61.6.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Isnberg G. Is potassium conductance of cardiac Purkinje fibres controlled by (Ca2+)? Nature. 1975 Jan 24;253(5489):273–274. doi: 10.1038/253273a0. [DOI] [PubMed] [Google Scholar]
  21. LIKOFF W. Cardiac arrhythmias complicating surgery. Am J Cardiol. 1959 Apr;3(4):427–429. doi: 10.1016/0002-9149(59)90362-5. [DOI] [PubMed] [Google Scholar]
  22. Lown B., Fakhro A. M., Hood W. B., Jr, Thorn G. W. The coronary care unit. New perspectives and directions. JAMA. 1967 Jan 16;199(3):188–198. [PubMed] [Google Scholar]
  23. NARAHASHI T., MOORE J. W., SCOTT W. R. TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS. J Gen Physiol. 1964 May;47:965–974. doi: 10.1085/jgp.47.5.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. NOBLE D. A modification of the Hodgkin--Huxley equations applicable to Purkinje fibre action and pace-maker potentials. J Physiol. 1962 Feb;160:317–352. doi: 10.1113/jphysiol.1962.sp006849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ochi R., Hashimoto K. The effect of procaine on the passive electrical properties of guinea-pig ventricular muscle. Pflugers Arch. 1978 Dec 15;378(1):1–7. doi: 10.1007/BF00581951. [DOI] [PubMed] [Google Scholar]
  26. SHANES A. M., FREYGANG W. H., GRUNDFEST H., AMATNIEK E. Anesthetic and calcium action in the voltage-clamped squid giant axon. J Gen Physiol. 1959 Mar 20;42(4):793–802. doi: 10.1085/jgp.42.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schwartz A., Lindenmayer G. E., Allen J. C. The sodium-potassium adenosine triphosphatase: pharmacological, physiological and biochemical aspects. Pharmacol Rev. 1975 Mar;27(01):3–134. [PubMed] [Google Scholar]
  28. Strichartz G. Molecular mechanisms of nerve block by local anesthetics. Anesthesiology. 1976 Oct;45(4):421–441. doi: 10.1097/00000542-197610000-00012. [DOI] [PubMed] [Google Scholar]
  29. TAYLOR R. E. Effect of procaine on electrical properties of squid axon membrane. Am J Physiol. 1959 May;196(5):1071–1078. doi: 10.1152/ajplegacy.1959.196.5.1071. [DOI] [PubMed] [Google Scholar]
  30. Thomas R. C. New design for sodium-sensitive glass micro-electrode. J Physiol. 1970 Sep;210(2):82P–83P. [PubMed] [Google Scholar]
  31. WEIDMANN S. Effects of calcium ions and local anesthetics on electrical properties of Purkinje fibres. J Physiol. 1955 Sep 28;129(3):568–582. doi: 10.1113/jphysiol.1955.sp005379. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES