Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1989 Aug;415:503–531. doi: 10.1113/jphysiol.1989.sp017734

Single sodium channels from canine ventricular myocytes: voltage dependence and relative rates of activation and inactivation.

M F Berman 1, J S Camardo 1, R B Robinson 1, S A Siegelbaum 1
PMCID: PMC1189189  PMID: 2561792

Abstract

1. Single sodium channel currents were recorded from canine ventricular myocytes in cell-attached patches. The relative rates of single-channel activation vs. inactivation as well as the voltage dependence of the rate of open-channel inactivation were studied. 2. Ensemble-averaged sodium currents showed relatively normal activation and inactivation kinetics, although the mid-point of the steady-state inactivation (h infinity) curve was shifted by 20-30 mV in the hyperpolarizing direction. This shift was due to the bath solution, which contained isotonic KCl to depolarize the cell to 0 mV. 3. Steady-state activation showed less of a voltage shift. The threshold for eliciting channel opening was around -70 mV and the mid-point of activation occurred near -50 mV. 4. The decline of the ensemble-averaged sodium current during a maintained depolarization was fitted by a single exponential function characterizing the apparent time constant of inactivation (tau h). The apparent rate of inactivation was voltage dependent, with tau h decreasing e-fold for a 15.4 mV depolarization. 5. The relative contributions of the rates of single-channel activation and inactivation in determining the time course of current decay (tau h) were examined using the approach of Aldrich, Corey & Stevens (1983). Mean channel open time (tau o) showed significant voltage dependence, increasing from 0.5 ms at -70 mV to around 0.8 ms at -40 mV. At -70 mV tau h was much greater than tau o, while at -40 mV the two time constants were similar. 6. The degree to which the kinetics of single-channel activation contribute to tau h was studied using the first latency distribution. The first latency function was fitted by two exponentials. The slow component was voltage dependent, decreasing from 19 ms at -70 mV to 0.5 ms at -40 mV. The fast component (0.1-0.5 ms) was not well resolved. 7. Comparing the first latency distribution with the time course of the ensemble-averaged sodium current at -40 mV showed that activation is nearly complete by the time of peak inward sodium current. However, at -70 mV, activation overlaps significantly with the apparent time course of inactivation of the ensemble-averaged current. 8. Using the methods of Aldrich et al. (1983) we also measured the apparent rate of open-channel closing (a) and open-channel inactivation (b). Both rates were voltage dependent, with a showing an e-fold decrease for an 11 mV depolarization and b showing an e-fold increase for a 30 mV depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Full text

PDF
505

Selected References

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

  1. Aldrich R. W., Corey D. P., Stevens C. F. A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature. 1983 Dec 1;306(5942):436–441. doi: 10.1038/306436a0. [DOI] [PubMed] [Google Scholar]
  2. Aldrich R. W., Stevens C. F. Voltage-dependent gating of single sodium channels from mammalian neuroblastoma cells. J Neurosci. 1987 Feb;7(2):418–431. doi: 10.1523/JNEUROSCI.07-02-00418.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Armstrong C. M., Bezanilla F. Inactivation of the sodium channel. II. Gating current experiments. J Gen Physiol. 1977 Nov;70(5):567–590. doi: 10.1085/jgp.70.5.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Cachelin A. B., De Peyer J. E., Kokubun S., Reuter H. Sodium channels in cultured cardiac cells. J Physiol. 1983 Jul;340:389–401. doi: 10.1113/jphysiol.1983.sp014768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colatsky T. J. Voltage clamp measurements of sodium channel properties in rabbit cardiac Purkinje fibres. J Physiol. 1980 Aug;305:215–234. doi: 10.1113/jphysiol.1980.sp013359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ebihara L., Johnson E. A. Fast sodium current in cardiac muscle. A quantitative description. Biophys J. 1980 Nov;32(2):779–790. doi: 10.1016/S0006-3495(80)85016-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fenwick E. M., Marty A., Neher E. Sodium and calcium channels in bovine chromaffin cells. J Physiol. 1982 Oct;331:599–635. doi: 10.1113/jphysiol.1982.sp014394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Fozzard H. A., Hanck D. A., Makielski J. C., Scanley B. E., Sheets M. F. Sodium channels in cardiac Purkinje cells. Experientia. 1987 Dec 1;43(11-12):1162–1168. doi: 10.1007/BF01945516. [DOI] [PubMed] [Google Scholar]
  11. Fozzard H. A., January C. T., Makielski J. C. New studies of the excitatory sodium currents in heart muscle. Circ Res. 1985 Apr;56(4):475–485. doi: 10.1161/01.res.56.4.475. [DOI] [PubMed] [Google Scholar]
  12. Gonoi T., Hille B. Gating of Na channels. Inactivation modifiers discriminate among models. J Gen Physiol. 1987 Feb;89(2):253–274. doi: 10.1085/jgp.89.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grant A. O., Starmer C. F. Mechanisms of closure of cardiac sodium channels in rabbit ventricular myocytes: single-channel analysis. Circ Res. 1987 Jun;60(6):897–913. doi: 10.1161/01.res.60.6.897. [DOI] [PubMed] [Google Scholar]
  14. Grant A. O., Starmer C. F., Strauss H. C. Unitary sodium channels in isolated cardiac myocytes of rabbit. Circ Res. 1983 Dec;53(6):823–829. doi: 10.1161/01.res.53.6.823. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hewett K., Legato M. J., Danilo P., Jr, Robinson R. B. Isolated myocytes from adult canine left ventricle: Ca2+ tolerance, electrophysiology, and ultrastructure. Am J Physiol. 1983 Nov;245(5 Pt 1):H830–H839. doi: 10.1152/ajpheart.1983.245.5.H830. [DOI] [PubMed] [Google Scholar]
  17. Horn R., Vandenberg C. A., Lange K. Statistical analysis of single sodium channels. Effects of N-bromoacetamide. Biophys J. 1984 Jan;45(1):323–335. doi: 10.1016/S0006-3495(84)84158-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Horn R., Vandenberg C. A. Statistical properties of single sodium channels. J Gen Physiol. 1984 Oct;84(4):505–534. doi: 10.1085/jgp.84.4.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Nilius B., Benndorf K., Markwardt F. Modified gating behaviour of aconitine treated single sodium channels from adult cardiac myocytes. Pflugers Arch. 1986 Dec;407(6):691–693. doi: 10.1007/BF00582653. [DOI] [PubMed] [Google Scholar]
  22. Noda M., Ikeda T., Kayano T., Suzuki H., Takeshima H., Kurasaki M., Takahashi H., Numa S. Existence of distinct sodium channel messenger RNAs in rat brain. Nature. 1986 Mar 13;320(6058):188–192. doi: 10.1038/320188a0. [DOI] [PubMed] [Google Scholar]
  23. Patlak J. B., Ortiz M. Slow currents through single sodium channels of the adult rat heart. J Gen Physiol. 1985 Jul;86(1):89–104. doi: 10.1085/jgp.86.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tseng G. N., Robinson R. B., Hoffman B. F. Passive properties and membrane currents of canine ventricular myocytes. J Gen Physiol. 1987 Nov;90(5):671–701. doi: 10.1085/jgp.90.5.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vandenberg C. A., Horn R. Inactivation viewed through single sodium channels. J Gen Physiol. 1984 Oct;84(4):535–564. doi: 10.1085/jgp.84.4.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yatani A., Kirsch G. E., Possani L. D., Brown A. M. Effects of New World scorpion toxins on single-channel and whole cell cardiac sodium currents. Am J Physiol. 1988 Mar;254(3 Pt 2):H443–H451. doi: 10.1152/ajpheart.1988.254.3.H443. [DOI] [PubMed] [Google Scholar]

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

RESOURCES