Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Jun 15;485(Pt 3):581–594. doi: 10.1113/jphysiol.1995.sp020754

Inactivation of the cardiac Na+ channels in guinea-pig ventricular cells through the open state.

T Mitsuiye 1, A Noma 1
PMCID: PMC1158029  PMID: 7562602

Abstract

1. The inactivation kinetics of the Na+ current were investigated using the improved oil-gap voltage clamp method in single ventricular cells of guinea-pig hearts. 2. Activation of the Na+ current was observed on depolarization more positive than -50 mV from a holding potential of -100 mV, and inactivation was complete during these depolarizations. The time course of current decay was fitted by a double exponential at potentials between -40 and -15 mV, and virtually by a single exponential at more positive potentials. The decay time courses examined either by the double-pulse protocol or the single-pulse protocol were similar. 3. The double-pulse protocol clearly revealed a sigmoidal onset of inactivation on depolarization. The initial delay of inactivation decreased with more positive potentials. The time course of double-pulse inactivation was reconstructed by integrating the Na+ current recorded by a continuous depolarization. 4. These findings are consistent with the hypothesis that the cardiac Na+ channel inactivates exclusively through the open state.

Full text

PDF
583

Selected References

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

  1. Benndorf K., Nilius B. Inactivation of sodium channels in isolated myocardial mouse cells. Eur Biophys J. 1987;15(2):117–127. doi: 10.1007/BF00257505. [DOI] [PubMed] [Google Scholar]
  2. Berman M. F., Camardo J. S., Robinson R. B., Siegelbaum S. A. Single sodium channels from canine ventricular myocytes: voltage dependence and relative rates of activation and inactivation. J Physiol. 1989 Aug;415:503–531. doi: 10.1113/jphysiol.1989.sp017734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bezanilla F., Armstrong C. M. Inactivation of the sodium channel. I. Sodium current experiments. J Gen Physiol. 1977 Nov;70(5):549–566. doi: 10.1085/jgp.70.5.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Follmer C. H., ten Eick R. E., Yeh J. Z. Sodium current kinetics in cat atrial myocytes. J Physiol. 1987 Mar;384:169–197. doi: 10.1113/jphysiol.1987.sp016449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gillespie J. I., Meves H. The time course of sodium inactivation in squid giant axons. J Physiol. 1980 Feb;299:289–307. doi: 10.1113/jphysiol.1980.sp013125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldman L., Schauf C. L. Quantitative description of sodium and potassium currents and computed action potentials in Myxicola giant axons. J Gen Physiol. 1973 Mar;61(3):361–384. doi: 10.1085/jgp.61.3.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Isenberg G., Klockner U. Calcium tolerant ventricular myocytes prepared by preincubation in a "KB medium". Pflugers Arch. 1982 Oct;395(1):6–18. doi: 10.1007/BF00584963. [DOI] [PubMed] [Google Scholar]
  9. Kimitsuki T., Mitsuiye T., Noma A. Maximum open probability of single Na+ channels during depolarization in guinea-pig cardiac cells. Pflugers Arch. 1990 Jul;416(5):493–500. doi: 10.1007/BF00382681. [DOI] [PubMed] [Google Scholar]
  10. Kimitsuki T., Mitsuiye T., Noma A. Negative shift of cardiac Na+ channel kinetics in cell-attached patch recordings. Am J Physiol. 1990 Jan;258(1 Pt 2):H247–H254. doi: 10.1152/ajpheart.1990.258.1.H247. [DOI] [PubMed] [Google Scholar]
  11. Kunze D. L., Lacerda A. E., Wilson D. L., Brown A. M. Cardiac Na currents and the inactivating, reopening, and waiting properties of single cardiac Na channels. J Gen Physiol. 1985 Nov;86(5):691–719. doi: 10.1085/jgp.86.5.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Makielski J. C., Sheets M. F., Hanck D. A., January C. T., Fozzard H. A. Sodium current in voltage clamped internally perfused canine cardiac Purkinje cells. Biophys J. 1987 Jul;52(1):1–11. doi: 10.1016/S0006-3495(87)83182-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mitsuiye T., Noma A. A new oil-gap method for internal perfusion and voltage clamp of single cardiac cells. Pflugers Arch. 1987 Sep;410(1-2):7–14. doi: 10.1007/BF00581889. [DOI] [PubMed] [Google Scholar]
  14. Mitsuiye T., Noma A. Exponential activation of the cardiac Na+ current in single guinea-pig ventricular cells. J Physiol. 1992;453:261–277. doi: 10.1113/jphysiol.1992.sp019228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mitsuiye T., Noma A. Quantification of exponential Na+ current activation in N-bromoacetamide-treated cardiac myocytes of guinea-pig. J Physiol. 1993 Jun;465:245–263. doi: 10.1113/jphysiol.1993.sp019675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nilius B. Modal gating behavior of cardiac sodium channels in cell-free membrane patches. Biophys J. 1988 Jun;53(6):857–862. doi: 10.1016/S0006-3495(88)83166-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nonner W. Relations between the inactivation of sodium channels and the immobilization of gating charge in frog myelinated nerve. J Physiol. 1980 Feb;299:573–603. doi: 10.1113/jphysiol.1980.sp013143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ono K., Fozzard H. A., Hanck D. A. Mechanism of cAMP-dependent modulation of cardiac sodium channel current kinetics. Circ Res. 1993 Apr;72(4):807–815. doi: 10.1161/01.res.72.4.807. [DOI] [PubMed] [Google Scholar]
  19. Oxford G. S., Pooler J. P. Selective modification of sodium channel gating in lobster axons by 2, 4, 6-trinitrophenol: Evidence for two inactivation mechanisms. J Gen Physiol. 1975 Dec;66(6):765–779. doi: 10.1085/jgp.66.6.765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Powell T., Terrar D. A., Twist V. W. Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol. 1980 May;302:131–153. doi: 10.1113/jphysiol.1980.sp013234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scanley B. E., Hanck D. A., Chay T., Fozzard H. A. Kinetic analysis of single sodium channels from canine cardiac Purkinje cells. J Gen Physiol. 1990 Mar;95(3):411–437. doi: 10.1085/jgp.95.3.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yue D. T., Lawrence J. H., Marban E. Two molecular transitions influence cardiac sodium channel gating. Science. 1989 Apr 21;244(4902):349–352. doi: 10.1126/science.2540529. [DOI] [PubMed] [Google Scholar]

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

RESOURCES