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. 1986 Mar;49(3):607–618. doi: 10.1016/S0006-3495(86)83688-8

Ion-channel entrances influence permeation. Net charge, size, shape, and binding considerations.

J A Dani
PMCID: PMC1329508  PMID: 2421791

Abstract

Many ion channels have wide entrances that serve as transition zones to the more selective narrow region of the pore. Here some physical features of these vestibules are explored. They are considered to have a defined size, funnel shape, and net-negative charge. Ion size, ionic screening of the negatively charged residues, cation binding, and blockage of current are analyzed to determine how the vestibules influence transport. These properties are coupled to an Eyring rate theory model for the narrow length of the pore. The results include the following: Wide vestibules allow the pore to have a short narrow region. Therefore, ions encounter a shorter length of restricted diffusion, and the channel conductance can be greater. The potential produced by the net-negative charge in the vestibules attracts cations into the pore. Since this potential varies with electrolyte concentration, the conductance measured at low electrolyte concentrations is larger than expected from measurements at high concentrations. Net charge inside the vestibules creates a local potential that confers some cation vs. anion, and divalent vs. monovalent selectivity. Large cations are less effective at screening (diminishing) the net-charge potential because they cannot enter the pore as well as small cations. Therefore, at an equivalent bulk concentration the attractive negative potential is larger, which causes large cations to saturate sites in the pore at lower concentrations. Small amounts of large or divalent cations can lead to misinterpretation of the permeation properties of a small monovalent cation.

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Selected References

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

  1. Apell H. J., Bamberg E., Alpes H., Läuger P. Formation of ion channels by a negatively charged analog of gramicidin A. J Membr Biol. 1977 Feb 24;31(1-2):171–188. doi: 10.1007/BF01869403. [DOI] [PubMed] [Google Scholar]
  2. Brisson A., Unwin P. N. Quaternary structure of the acetylcholine receptor. Nature. 1985 Jun 6;315(6019):474–477. doi: 10.1038/315474a0. [DOI] [PubMed] [Google Scholar]
  3. Cooper K., Jakobsson E., Wolynes P. The theory of ion transport through membrane channels. Prog Biophys Mol Biol. 1985;46(1):51–96. doi: 10.1016/0079-6107(85)90012-4. [DOI] [PubMed] [Google Scholar]
  4. Dwyer T. M., Adams D. J., Hille B. The permeability of the endplate channel to organic cations in frog muscle. J Gen Physiol. 1980 May;75(5):469–492. doi: 10.1085/jgp.75.5.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eisenman G., Sandblom J., Neher E. Interactions in cation permeation through the gramicidin channel. Cs, Rb, K, Na, Li, Tl, H, and effects of anion binding. Biophys J. 1978 May;22(2):307–340. doi: 10.1016/S0006-3495(78)85491-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Finer-Moore J., Stroud R. M. Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor. Proc Natl Acad Sci U S A. 1984 Jan;81(1):155–159. doi: 10.1073/pnas.81.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fischer W., Brickmann J., Läuger P. Molecular dynamics study of ion transport in transmembrane protein channels. Biophys Chem. 1981 Apr;13(2):105–116. doi: 10.1016/0301-4622(81)80009-9. [DOI] [PubMed] [Google Scholar]
  8. Frehland E. Theory of transport noise in membrane channels with open-closed kinetics. Biophys Struct Mech. 1979 Mar 21;5(1):91–106. doi: 10.1007/BF00535775. [DOI] [PubMed] [Google Scholar]
  9. French R. J., Shoukimas J. J. An ion's view of the potassium channel. The structure of the permeation pathway as sensed by a variety of blocking ions. J Gen Physiol. 1985 May;85(5):669–698. doi: 10.1085/jgp.85.5.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GRAHAME D. C. The electrical double layer and the theory of electrocapillarity. Chem Rev. 1947 Dec;41(3):441–501. doi: 10.1021/cr60130a002. [DOI] [PubMed] [Google Scholar]
  11. Gilbert D. L., Ehrenstein G. Effect of divalent cations on potassium conductance of squid axons: determination of surface charge. Biophys J. 1969 Mar;9(3):447–463. doi: 10.1016/S0006-3495(69)86396-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Guy H. R. A structural model of the acetylcholine receptor channel based on partition energy and helix packing calculations. Biophys J. 1984 Jan;45(1):249–261. doi: 10.1016/S0006-3495(84)84152-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Hille B., Woodhull A. M., Shapiro B. I. Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH. Philos Trans R Soc Lond B Biol Sci. 1975 Jun 10;270(908):301–318. doi: 10.1098/rstb.1975.0011. [DOI] [PubMed] [Google Scholar]
  15. Huang L. Y., Catterall W. A., Ehrenstein G. Selectivity of cations and nonelectrolytes for acetylcholine-activated channels in cultured muscle cells. J Gen Physiol. 1978 Apr;71(4):397–410. doi: 10.1085/jgp.71.4.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kistler J., Stroud R. M., Klymkowsky M. W., Lalancette R. A., Fairclough R. H. Structure and function of an acetylcholine receptor. Biophys J. 1982 Jan;37(1):371–383. doi: 10.1016/S0006-3495(82)84685-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Latorre R., Miller C. Conduction and selectivity in potassium channels. J Membr Biol. 1983;71(1-2):11–30. doi: 10.1007/BF01870671. [DOI] [PubMed] [Google Scholar]
  18. Lee W. K., Jordan P. C. Molecular dynamics simulation of cation motion in water-filled gramicidinlike pores. Biophys J. 1984 Dec;46(6):805–819. doi: 10.1016/S0006-3495(84)84079-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Levitt D. G. Comparison of Nernst-Planck and reaction rate models for multiply occupied channels. Biophys J. 1982 Mar;37(3):575–587. [PMC free article] [PubMed] [Google Scholar]
  20. Levitt D. G. Strong electrolyte continuum theory solution for equilibrium profiles, diffusion limitation, and conductance in charged ion channels. Biophys J. 1985 Jul;48(1):19–31. doi: 10.1016/S0006-3495(85)83757-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Läuger P., Stephan W., Frehland E. Fluctuations of barrier structure in ionic channels. Biochim Biophys Acta. 1980 Oct 16;602(1):167–180. doi: 10.1016/0005-2736(80)90299-0. [DOI] [PubMed] [Google Scholar]
  22. Mackay D. H., Berens P. H., Wilson K. R., Hagler A. T. Structure and dynamics of ion transport through gramicidin A. Biophys J. 1984 Aug;46(2):229–248. doi: 10.1016/S0006-3495(84)84016-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Maeno T., Edwards C., Anraku M. Permeability of the endplate membrane activated by acetylcholine to some organic cations. J Neurobiol. 1977 Mar;8(2):173–184. doi: 10.1002/neu.480080208. [DOI] [PubMed] [Google Scholar]
  24. McLaughlin S. G., Szabo G., Eisenman G. Divalent ions and the surface potential of charged phospholipid membranes. J Gen Physiol. 1971 Dec;58(6):667–687. doi: 10.1085/jgp.58.6.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mishina M., Tobimatsu T., Imoto K., Tanaka K., Fujita Y., Fukuda K., Kurasaki M., Takahashi H., Morimoto Y., Hirose T. Location of functional regions of acetylcholine receptor alpha-subunit by site-directed mutagenesis. 1985 Jan 31-Feb 6Nature. 313(6001):364–369. doi: 10.1038/313364a0. [DOI] [PubMed] [Google Scholar]
  26. Noda M., Shimizu S., Tanabe T., Takai T., Kayano T., Ikeda T., Takahashi H., Nakayama H., Kanaoka Y., Minamino N. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature. 1984 Nov 8;312(5990):121–127. doi: 10.1038/312121a0. [DOI] [PubMed] [Google Scholar]
  27. Noda M., Takahashi H., Tanabe T., Toyosato M., Kikyotani S., Furutani Y., Hirose T., Takashima H., Inayama S., Miyata T. Structural homology of Torpedo californica acetylcholine receptor subunits. Nature. 1983 Apr 7;302(5908):528–532. doi: 10.1038/302528a0. [DOI] [PubMed] [Google Scholar]
  28. Oxford G. S., Yeh J. Z. Interactions of monovalent cations with sodium channels in squid axon. I. Modification of physiological inactivation gating. J Gen Physiol. 1985 Apr;85(4):583–602. doi: 10.1085/jgp.85.4.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. White M. M., Mayne K. M., Lester H. A., Davidson N. Mouse-Torpedo hybrid acetylcholine receptors: functional homology does not equal sequence homology. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4852–4856. doi: 10.1073/pnas.82.14.4852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Young E. F., Ralston E., Blake J., Ramachandran J., Hall Z. W., Stroud R. M. Topological mapping of acetylcholine receptor: evidence for a model with five transmembrane segments and a cytoplasmic COOH-terminal peptide. Proc Natl Acad Sci U S A. 1985 Jan;82(2):626–630. doi: 10.1073/pnas.82.2.626. [DOI] [PMC free article] [PubMed] [Google Scholar]

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