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. 1979 Feb 1;73(2):139–157. doi: 10.1085/jgp.73.2.139

4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers

PMCID: PMC2215238  PMID: 220376

Abstract

We have studied the effects of the potassium-blocking agent 4- aminopyridine (4-AP) on the action potential and membrane currents of the sheep cardiac Purkinje fiber. 4-AP slowed the rate of phase 1 repolarization and shifted the plateau of the action potential to less negative potentials. In the presence of 4-AP, the substitution of sodium methylsulfate or methanesulfonate for the NaCl of Tyrode's solution further slowed the rate of phase 1 repolarization, even though chloride replacement has no effect on the untreated preparation. In voltage clamp experiments, 4-AP rapidly and reversibly reduced the early peak of outward current that is seen when the Purkinje fiber membrane is voltage-clamped to potentials positive to -20 mV. In addition, 4-AP reduced the steady outward current seen at the end of clamp steps positive to -40 mV. 4-AP did not appear to change the slow inward current observed over the range of -60 to -40 mV, nor did it greatly change the current tails that have been used as a measure of the slow inward conductance at more positive potentials. 4-AP did not block the inward rectifying potassium currents, IK1 and IK2. A phasic outward current component that was insensitive to 4-AP was reduced by chloride replacement. We conclude that the early outward current has two components: a chloride-sensitive component plus a 4-AP-sensitive component. Since a portion of the steady-state current was sensitive to 4-AP, the early outward current either does not fully inactivate or 4- AP blocks a component of time-independent background current.

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Selected References

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  1. Adrian R. H., Chandler W. K., Hodgkin A. L. Voltage clamp experiments in skeletal muscle fibres. J Physiol. 1966 Oct;186(2):51P–52P. [PubMed] [Google Scholar]
  2. Armstrong C. M. Ionic pores, gates, and gating currents. Q Rev Biophys. 1974 May;7(2):179–210. doi: 10.1017/s0033583500001402. [DOI] [PubMed] [Google Scholar]
  3. Beeler G. W., Reuter H. Reconstruction of the action potential of ventricular myocardial fibres. J Physiol. 1977 Jun;268(1):177–210. doi: 10.1113/jphysiol.1977.sp011853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carmeliet E., Verdonck F. Reduction of potassium permeability by chloride substitution in cardiac cells. J Physiol. 1977 Feb;265(1):193–206. doi: 10.1113/jphysiol.1977.sp011712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Connor J. A., Stevens C. F. Voltage clamp studies of a transient outward membrane current in gastropod neural somata. J Physiol. 1971 Feb;213(1):21–30. doi: 10.1113/jphysiol.1971.sp009365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dudel J., Peper K., Rüdel R., Trautwein W. The dynamic chloride component of membrane current in Purkinje fibers. Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;295(3):197–212. doi: 10.1007/BF01844100. [DOI] [PubMed] [Google Scholar]
  7. Ehrenstein G., Gilbert D. L. Slow changes of potassium permeability in the squid giant axon. Biophys J. 1966 Sep;6(5):553–566. doi: 10.1016/S0006-3495(66)86677-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FASTIER F. N., McDOWALL M. A. A comparison of the pharmacological properties of the three isomeric aminopyridines. Aust J Exp Biol Med Sci. 1958 Aug;36(4):365–371. doi: 10.1038/icb.1958.39. [DOI] [PubMed] [Google Scholar]
  9. Fozzard H. A., Hiraoka M. The positive dynamic current and its inactivation properties in cardiac Purkinje fibres. J Physiol. 1973 Nov;234(3):569–586. doi: 10.1113/jphysiol.1973.sp010361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gibbons W. R., Fozzard H. A. Relationships between voltage and tension in sheep cardiac Purkinje fibers. J Gen Physiol. 1975 Mar;65(3):345–365. doi: 10.1085/jgp.65.3.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HALDIMANN C. EFFET DU T'ETRA'ETHYLAMMONIUM SUR LES POTENTIELS DE REPOS ET D'ACTION DU COEUR DE MOUTON. Arch Int Pharmacodyn Ther. 1963 Nov 1;146:1–9. [PubMed] [Google Scholar]
  12. Hiraoka M., Hiraoka M. The role of the positive dynamic current on the action potential of cardiac Purkinje fibers. Jpn J Physiol. 1975;25(6):705–717. doi: 10.2170/jjphysiol.25.705. [DOI] [PubMed] [Google Scholar]
  13. Isenberg G. Cardiac Purkinje fibers: cesium as a tool to block inward rectifying potassium currents. Pflugers Arch. 1976 Sep 30;365(2-3):99–106. doi: 10.1007/BF01067006. [DOI] [PubMed] [Google Scholar]
  14. Kass R. S., Tsien R. W. Control of action potential duration by calcium ions in cardiac Purkinje fibers. J Gen Physiol. 1976 May;67(5):599–617. doi: 10.1085/jgp.67.5.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kenyon J. L., Gibbons W. R. Effects of low-chloride solutions on action potentials of sheep cardiac Purkinje fibers. J Gen Physiol. 1977 Nov;70(5):635–660. doi: 10.1085/jgp.70.5.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kenyon J. L., Gibbons W. R. Influence of chloride, potassium, and tetraethylammonium on the early outward current of sheep cardiac Purkinje fibers. J Gen Physiol. 1979 Feb;73(2):117–138. doi: 10.1085/jgp.73.2.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lemeignan M., Auclair M. C., Rodallec A., Lechat P. Analyse electrophysiologique des effets de l'amino-4 pyridine sur le lambeau ventricularie isolé de coeur de cobaye. Arch Int Pharmacodyn Ther. 1975 Jul;216(1):165–176. [PubMed] [Google Scholar]
  18. McAllister R. E., Noble D. The time and voltage dependence of the slow outward current in cardiac Purkinje fibres. J Physiol. 1966 Oct;186(3):632–662. doi: 10.1113/jphysiol.1966.sp008060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McAllister R. E., Noble D., Tsien R. W. Reconstruction of the electrical activity of cardiac Purkinje fibres. J Physiol. 1975 Sep;251(1):1–59. doi: 10.1113/jphysiol.1975.sp011080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Meves H., Pichon Y. The effect of internal and external 4-aminopyridine on the potassium currents in intracellularly perfused squid giant axons. J Physiol. 1977 Jun;268(2):511–532. doi: 10.1113/jphysiol.1977.sp011869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. NAKAJIMA S., IWASAKI S., OBATA K. Delayed rectification and anomalous rectification in frog's skeletal muscle membrane. J Gen Physiol. 1962 Sep;46:97–115. doi: 10.1085/jgp.46.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Noble D., Tsien R. W. Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres. J Physiol. 1969 Jan;200(1):205–231. doi: 10.1113/jphysiol.1969.sp008689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Peper K., Trautwein W. A membrane current related to the plateau of the action potential of Purkinje fibers. Pflugers Arch. 1968;303(2):108–123. doi: 10.1007/BF00592629. [DOI] [PubMed] [Google Scholar]
  24. Reuter H. The dependence of slow inward current in Purkinje fibres on the extracellular calcium-concentration. J Physiol. 1967 Sep;192(2):479–492. doi: 10.1113/jphysiol.1967.sp008310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schauf C. L., Colton C. A., Colton J. S., Davis F. A. Aminopyridines and sparteine as inhibitors of membrane potassium conductance: effects on Myxicola giant axons and the lobster neuromuscular junction. J Pharmacol Exp Ther. 1976 May;197(2):414–425. [PubMed] [Google Scholar]
  26. Siegelbaum S. A., Tsien R. W., Kass R. S. Role of intracellular calcium in the transient outward current of calf Purkinje fibres. Nature. 1977 Oct 13;269(5629):611–613. doi: 10.1038/269611a0. [DOI] [PubMed] [Google Scholar]
  27. Vitek M., Trautwein W. Slow inward current and action potential in cardiac Purkinje fibres. The effect of Mn plus,plus-ions. Pflugers Arch. 1971;323(3):204–218. doi: 10.1007/BF00586384. [DOI] [PubMed] [Google Scholar]
  28. Woodbury J. W., Miles P. R. Anion conductance of frog muscle membranes: one channel, two kinds of pH dependence. J Gen Physiol. 1973 Sep;62(3):324–353. doi: 10.1085/jgp.62.3.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yeh J. Z., Oxford G. S., Wu C. H., Narahashi T. Dynamics of aminopyridine block of potassium channels in squid axon membrane. J Gen Physiol. 1976 Nov;68(5):519–535. doi: 10.1085/jgp.68.5.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yeh J. Z., Oxford G. S., Wu C. H., Narahashi T. Interactions of aminopyridines with potassium channels of squid axon membranes. Biophys J. 1976 Jan;16(1):77–81. doi: 10.1016/S0006-3495(76)85663-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

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