Abstract
Brownian dynamics simulations have been carried out to study the transport of ions in a vestibular geometry, which offers a more realistic shape for membrane channels than cylindrical tubes. Specifically, we consider a torus-shaped channel, for which the analytical solution of Poisson's equation is possible. The system is composed of the toroidal channel, with length and radius of the constricted region of 80 A and 4 A, respectively, and two reservoirs containing 50 sodium ions and 50 chloride ions. The positions of each of these ions executing Brownian motion under the influence of a stochastic force and a systematic electric force are determined at discrete time steps of 50 fs for up to 2.5 ns. All of the systematic forces acting on an ion due to the other ions, an external electric field, fixed charges in the channel protein, and the image charges induced at the water-protein boundary are explicitly included in the calculations. We find that the repulsive dielectric force arising from the induced surface charges plays a dominant role in channel dynamics. It expels an ion from the vestibule when it is deliberately put in it. Even in the presence of an applied electric potential of 100 mV, an ion cannot overcome this repulsive force and permeate the channel. Only when dipoles of a favorable orientation are placed along the sides of the transmembrane segment can an ion traverse the channel under the influence of a membrane potential. When the strength of the dipoles is further increased, an ion becomes detained in a potential well, and the driving force provided by the applied field is not sufficient to drive the ion out of the well. The trajectory of an ion navigating across the channel mostly remains close to the central axis of the pore lumen. Finally, we discuss the implications of these findings for the transport of ions across the membrane.
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- Bek S., Jakobsson E. Brownian dynamics study of a multiply-occupied cation channel: application to understanding permeation in potassium channels. Biophys J. 1994 Apr;66(4):1028–1038. doi: 10.1016/S0006-3495(94)80884-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen D., Lear J., Eisenberg B. Permeation through an open channel: Poisson-Nernst-Planck theory of a synthetic ionic channel. Biophys J. 1997 Jan;72(1):97–116. doi: 10.1016/S0006-3495(97)78650-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chiu S. W., Jakobsson E. Stochastic theory of singly occupied ion channels. II. Effects of access resistance and potential gradients extending into the bath. Biophys J. 1989 Jan;55(1):147–157. doi: 10.1016/S0006-3495(89)82786-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chiu S. W., Subramaniam S., Jakobsson E., McCammon J. A. Water and polypeptide conformations in the gramicidin channel. A molecular dynamics study. Biophys J. 1989 Aug;56(2):253–261. doi: 10.1016/S0006-3495(89)82671-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chung S. H., Kuyucak S. Changes in the kinetics and conductance of N-methyl-D-aspartate (NMDA)-receptor activated single channels with temperature. Neurosci Lett. 1995 Mar 10;187(3):181–184. doi: 10.1016/0304-3940(95)11369-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Hoyles M., Kuyucak S., Chung S. H. Energy barrier presented to ions by the vestibule of the biological membrane channel. Biophys J. 1996 Apr;70(4):1628–1642. doi: 10.1016/S0006-3495(96)79726-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jakobsson E., Chiu S. W. Stochastic theory of ion movement in channels with single-ion occupancy. Application to sodium permeation of gramicidin channels. Biophys J. 1987 Jul;52(1):33–45. doi: 10.1016/S0006-3495(87)83186-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jordan P. C., Bacquet R. J., McCammon J. A., Tran P. How electrolyte shielding influences the electrical potential in transmembrane ion channels. Biophys J. 1989 Jun;55(6):1041–1052. doi: 10.1016/S0006-3495(89)82903-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jordan P. C. How pore mouth charge distributions alter the permeability of transmembrane ionic channels. Biophys J. 1987 Feb;51(2):297–311. doi: 10.1016/S0006-3495(87)83336-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuyucak S., Chung S. H. Temperature dependence of conductivity in electrolyte solutions and ionic channels of biological membranes. Biophys Chem. 1994 Sep;52(1):15–24. doi: 10.1016/0301-4622(94)00034-4. [DOI] [PubMed] [Google Scholar]
- 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]
- Milburn T., Saint D. A., Chung S. H. The temperature dependence of conductance of the sodium channel: implications for mechanisms of ion permeation. Receptors Channels. 1995;3(3):201–211. [PubMed] [Google Scholar]
- Roux B., Karplus M. Ion transport in a model gramicidin channel. Structure and thermodynamics. Biophys J. 1991 May;59(5):961–981. doi: 10.1016/S0006-3495(91)82311-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toyoshima C., Unwin N. Ion channel of acetylcholine receptor reconstructed from images of postsynaptic membranes. Nature. 1988 Nov 17;336(6196):247–250. doi: 10.1038/336247a0. [DOI] [PubMed] [Google Scholar]