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. 1980 Nov;77(11):6582–6586. doi: 10.1073/pnas.77.11.6582

Kinetic models suggest bimolecular reaction steps in axonal Na+-channel gating.

P L Dorogi, E Neumann
PMCID: PMC350330  PMID: 6256748

Abstract

Abstract kinetic models that can successfully simulate the ion-permeability features of axonal Na+ channels suggest the presence of bimolecular reaction steps in the activation of the channels. A chemically plausible interpretation of minimum complexity is described. The implied chemical formalism is highly suggestive of an activator-controlled gating system with strong similarities to the acetylcholine-regulated system. Conformational changes that underlie the ion-conductance changes are suggested to possess a greater sensitivity to the membrane field in axonal parts of excitable membranes than at synaptic parts. This would allow axonal permeability changes to be energetically regulated more conservatively than is observed for synaptic ion channels. Axonal K+ channels with delayed activation kinetics would serve to reverse the increase in membrane permeability to Na+ with a minimum of chemical dissipation.

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Selected References

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

  1. Chester J., Lentz T. L., Marquis J. K., Mautner H. G. Localization of horseradish peroxidase-alpha-bungarotoxin binding in crustacean axonal membrane vesicles and intact axons. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3542–3546. doi: 10.1073/pnas.76.7.3542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Gage P. W., Armstrong C. M. Miniature end-plate currents in voltage-clamped muscle fibre. Nature. 1968 Apr 27;218(5139):363–365. doi: 10.1038/218363b0. [DOI] [PubMed] [Google Scholar]
  3. Gage P. W. Generation of end-plate potentials. Physiol Rev. 1976 Jan;56(1):177–247. doi: 10.1152/physrev.1976.56.1.177. [DOI] [PubMed] [Google Scholar]
  4. Gage P. W., McBurney R. N. Effects of membrane potential, temperature and neostigmine on the conductance change caused by a quantum or acetylcholine at the toad neuromuscular junction. J Physiol. 1975 Jan;244(2):385–407. doi: 10.1113/jphysiol.1975.sp010805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldman L. Quantitative description of the sodium conductance of the giant axon of Myxicola in terms of a generalized second-order variable. Biophys J. 1975 Feb;15(2 Pt 1):119–136. doi: 10.1016/s0006-3495(75)85796-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldman L., Schauf C. L. Inactivation of the sodium current in Myxicola giant axons. Evidence for coupling to the activation process. J Gen Physiol. 1972 Jun;59(6):659–675. doi: 10.1085/jgp.59.6.659. [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. Hoskin F. C. Anaerobic glycolysis in parts of the giant axon of squid. Nature. 1966 May 21;210(5038):856–857. doi: 10.1038/210856a0. [DOI] [PubMed] [Google Scholar]
  9. Jakobsson E. A fully coupled transient excited state model for the sodium channel. I. Conductance in the voltage clamped case. J Math Biol. 1978 Mar 3;5(2):121–142. doi: 10.1007/BF00275895. [DOI] [PubMed] [Google Scholar]
  10. Jakobsson E. An assessment of a coupled three-state kinetic model for sodium conductance changes. Biophys J. 1976 Apr;16(4):291–301. doi: 10.1016/S0006-3495(76)85689-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jakobsson E. The physical interpretation of mathematical models for sodium permeability changes in excitable membranes. Biophys J. 1973 Nov;13(11):1200–1211. doi: 10.1016/S0006-3495(73)86055-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Magleby K. L., Stevens C. F. The effect of voltage on the time course of end-plate currents. J Physiol. 1972 May;223(1):151–171. doi: 10.1113/jphysiol.1972.sp009839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. NACHMANSOHN D. Metabolism and function of the nerve cell. Harvey Lect. 1953;49:57–99. [PubMed] [Google Scholar]
  14. Neumann E., Nachmansohn D., Katchalsky A. An attempt at an integral interpretation of nerve excitability. Proc Natl Acad Sci U S A. 1973 Mar;70(3):727–731. doi: 10.1073/pnas.70.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rang H. P., Ritter J. M. A new kind of drug antagonism: evidence that agonists cause a molecular change in acetylcholine receptors. Mol Pharmacol. 1969 Jul;5(4):394–411. [PubMed] [Google Scholar]
  16. Rawlings P. K., Neumann E. Physical-chemical approach to the transient change in Na ion conductivity of excitable membranes. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4492–4496. doi: 10.1073/pnas.73.12.4492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schoffeniels E., Dandrifosse G. Protein phosphorylation and sodium conductance in nerve membrane. Proc Natl Acad Sci U S A. 1980 Feb;77(2):812–816. doi: 10.1073/pnas.77.2.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Villegas G. M., Villegas R. Ultrastructural studies of the squid nerve fibers. J Gen Physiol. 1968 May;51(5 Suppl):44S+–44S+. [PubMed] [Google Scholar]

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