Skip to main content
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1988 Oct 1;92(4):413–430. doi: 10.1085/jgp.92.4.413

Sodium channel subconductance levels measured with a new variance-mean analysis

PMCID: PMC2228911  PMID: 2849627

Abstract

The currents through single Na+ channels were recorded from dissociated cells of the flexor digitorum brevis muscle of the mouse. At 15 degrees C the prolonged bursts of Na+ channel openings produced by application of the drug DPI 201-106 had brief sojourns to subconductance levels. The subconductance events were relatively rare and brief, but could be identified using a new technique that sorts amplitude estimates based on their variance. The resulting "levels histogram" had a resolution of the conductance levels during channel activity that was superior to that of standard amplitude histograms. Cooling the preparation to 0 degrees C prolonged the subconductance events, and permitted further quantitative analysis of their amplitudes, as well as clear observations of single-channel subconductance events from untreated Na+ channels. In all cases the results were similar: a subconductance level, with an amplitude of roughly 35% of the fully open conductance and similar reversal potential, was present in both drug-treated and normal Na+ channels. Drug-treated channels spent approximately 3-6% of their total open time in the subconductance state over a range of potentials that caused the open probability to vary between 0.1 and 0.9. The summed levels histograms from many channels had a distinctive form, with broader, asymmetrical open and substate distributions compared with those of the closed state. Individual subconductance events to levels other than the most common 35% were also observed. I conclude that subconductance events are a normal subset of the open state of Na+ channels, whether or not they are drug treated. The subconductance events may represent a conformational alteration of the channel that occurs when it conducts ions.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Auerbach A., Sachs F. Flickering of a nicotinic ion channel to a subconductance state. Biophys J. 1983 Apr;42(1):1–10. doi: 10.1016/S0006-3495(83)84362-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Chinn K., Narahashi T. Stabilization of sodium channel states by deltamethrin in mouse neuroblastoma cells. J Physiol. 1986 Nov;380:191–207. doi: 10.1113/jphysiol.1986.sp016280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colquhoun D., Sakmann B. Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. J Physiol. 1985 Dec;369:501–557. doi: 10.1113/jphysiol.1985.sp015912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cull-Candy S. G., Usowicz M. M. Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature. 1987 Feb 5;325(6104):525–528. doi: 10.1038/325525a0. [DOI] [PubMed] [Google Scholar]
  6. Garber S. S., Miller C. Single Na+ channels activated by veratridine and batrachotoxin. J Gen Physiol. 1987 Mar;89(3):459–480. doi: 10.1085/jgp.89.3.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gordon L. G., Haydon D. A. The unit conductance channel of alamethicin. Biochim Biophys Acta. 1972 Mar 17;255(3):1014–1018. doi: 10.1016/0005-2736(72)90415-4. [DOI] [PubMed] [Google Scholar]
  8. Green W. N., Weiss L. B., Andersen O. S. Batrachotoxin-modified sodium channels in planar lipid bilayers. Ion permeation and block. J Gen Physiol. 1987 Jun;89(6):841–872. doi: 10.1085/jgp.89.6.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hamill O. P., Bormann J., Sakmann B. Activation of multiple-conductance state chloride channels in spinal neurones by glycine and GABA. 1983 Oct 27-Nov 2Nature. 305(5937):805–808. doi: 10.1038/305805a0. [DOI] [PubMed] [Google Scholar]
  10. Hamill O. P., Sakmann B. Multiple conductance states of single acetylcholine receptor channels in embryonic muscle cells. Nature. 1981 Dec 3;294(5840):462–464. doi: 10.1038/294462a0. [DOI] [PubMed] [Google Scholar]
  11. Hunter M., Giebisch G. Multi-barrelled K channels in renal tubules. Nature. 1987 Jun 11;327(6122):522–524. doi: 10.1038/327522a0. [DOI] [PubMed] [Google Scholar]
  12. Jahr C. E., Stevens C. F. Glutamate activates multiple single channel conductances in hippocampal neurons. Nature. 1987 Feb 5;325(6104):522–525. doi: 10.1038/325522a0. [DOI] [PubMed] [Google Scholar]
  13. Kohlhardt M., Fröbe U., Herzig J. W. Modification of single cardiac Na+ channels by DPI 201-106. J Membr Biol. 1986;89(2):163–172. doi: 10.1007/BF01869712. [DOI] [PubMed] [Google Scholar]
  14. Krouse M. E., Schneider G. T., Gage P. W. A large anion-selective channel has seven conductance levels. Nature. 1986 Jan 2;319(6048):58–60. doi: 10.1038/319058a0. [DOI] [PubMed] [Google Scholar]
  15. Labarca P. P., Miller C. A K+-selective, three-state channel from fragmented sarcoplasmic reticulum of frog leg muscle. J Membr Biol. 1981;61(1):31–38. doi: 10.1007/BF01870750. [DOI] [PubMed] [Google Scholar]
  16. Latorre R., Alvarez O. Voltage-dependent channels in planar lipid bilayer membranes. Physiol Rev. 1981 Jan;61(1):77–150. doi: 10.1152/physrev.1981.61.1.77. [DOI] [PubMed] [Google Scholar]
  17. Nagy K., Kiss T., Hof D. Single Na channels in mouse neuroblastoma cell membrane. Indications for two open states. Pflugers Arch. 1983 Dec;399(4):302–308. doi: 10.1007/BF00652757. [DOI] [PubMed] [Google Scholar]
  18. Nagy K. Subconductance states of single sodium channels modified by chloramine-T and sea anemone toxin in neuroblastoma cells. Eur Biophys J. 1987;15(3):129–132. doi: 10.1007/BF00263676. [DOI] [PubMed] [Google Scholar]
  19. Neher E., Sakmann B. Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature. 1976 Apr 29;260(5554):799–802. doi: 10.1038/260799a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Patlak J. B., Ortiz M. Two modes of gating during late Na+ channel currents in frog sartorius muscle. J Gen Physiol. 1986 Feb;87(2):305–326. doi: 10.1085/jgp.87.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Prod'hom B., Pietrobon D., Hess P. Direct measurement of proton transfer rates to a group controlling the dihydropyridine-sensitive Ca2+ channel. Nature. 1987 Sep 17;329(6136):243–246. doi: 10.1038/329243a0. [DOI] [PubMed] [Google Scholar]
  23. Romey G., Quast U., Pauron D., Frelin C., Renaud J. F., Lazdunski M. Na+ channels as sites of action of the cardioactive agent DPI 201-106 with agonist and antagonist enantiomers. Proc Natl Acad Sci U S A. 1987 Feb;84(3):896–900. doi: 10.1073/pnas.84.3.896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scanley B. E., Fozzard H. A. Low conductance sodium channels in canine cardiac Purkinje cells. Biophys J. 1987 Sep;52(3):489–495. doi: 10.1016/S0006-3495(87)83237-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scholtysik G., Salzmann R., Berthold R., Herzig J. W., Quast U., Markstein R. DPI 201-106, a novel cardioactive agent. Combination of cAMP-independent positive inotropic, negative chronotropic, action potential prolonging and coronary dilatory properties. Naunyn Schmiedebergs Arch Pharmacol. 1985 May;329(3):316–325. doi: 10.1007/BF00501887. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Weiss R. E., Horn R. Single-channel studies of TTX-sensitive and TTX-resistant sodium channels in developing rat muscle reveal different open channel properties. Ann N Y Acad Sci. 1986;479:152–161. doi: 10.1111/j.1749-6632.1986.tb15567.x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of General Physiology are provided here courtesy of The Rockefeller University Press

RESOURCES