Skip to main content
SpringerLink
Log in

Influence of interionic interactions on functional state and blocker binding of voltage-gated potassium channels

  • Published:
Moscow University Biological Sciences Bulletin Aims and scope Submit manuscript

Abstract

A mechanism of ion conduction of a voltage-gated potassium channel KcsA was investigated in full-atomic approximation at a trajectory length of 100 ns using the Lomonosov supercomputer. Methods of molecular dynamics were employed. A structure of the KcsA channel in the open state obtained by X-ray structure analysis (PDB ID 3fb7) was used. Free energy profiles of the KcsA pore occupied with either one or three potassium ions were calculated. It was shown that, under physiological conditions, ions pass through the channel pore cooperatively and the mechanism most probably includes three ions permeating in concert. Interactions of the mammalian voltage-gated channel Kv1.2 with neurotoxin were investigated. It was demonstrated that the effect of interionic interactions on binding of a blocker is rather insufficient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Molecular Dynamics Simulations of Potassium Channels, Centr. Eur. J. Chem., 2007, vol. 5, pp. 635–671.

  2. Jensen, M., Borhani, D., Lindorff-Larsen, K., Maragakis, P., Jogini, V., Eastwood, M., Dror, R., and Shaw, D., Principles of Conduction and Hydrophobic Gating in K+ Channels, Proc. Natl. Acad. Sci. USA, 2010, vol. 107, pp. 5833–5838.

    Article  PubMed  CAS  Google Scholar 

  3. Berneche, S. and Roux, B., Energetics of Ion Conduction through the K+ Channel, Nature, 2001, vol. 414, pp. 73–77.

    Article  PubMed  CAS  Google Scholar 

  4. Khalili-Araghi, F., Tajkhorshid, E., and Schulten, K., Dynamics of K+ Ion Conduction through Kvl. 2, Biophys. J., 2006, vol. 91, pp. L72–L74.

    Article  PubMed  CAS  Google Scholar 

  5. Sokolova, O.S., Shaitan, K.V., Grizel’, A.V., Popinako, A.V., Karlova, M.G., and Kirpichnikov, M.P., Three-Dimensional Structure of Human VoltageGated Ion Channel Kv10.2 Studied by Electron Microscopy of Macromolecules and Molecular Modeling, Russ. J. Bioorg. Chem., 2012, vol. 38, no. 2, pp. 152–158.

    Article  CAS  Google Scholar 

  6. Boiteux, C., Kraszewski, S., Ramseyer, C., Girarder, C., Ion Conductance Vs. Pore Gating and Selectivity in KcsA Channel: Modeling Achievements and Perspectives, J. Mol. Mod., 2007, vol. 13, pp. 699–713.

    Article  CAS  Google Scholar 

  7. Cuello, L., Jogini, V., Cortes, M., and Perozo, E., Structural Mechanism of C-Type Inactivation in K+ Channels, Nature, 2010, vol. 466, pp. 203–208.

    Article  PubMed  CAS  Google Scholar 

  8. Smart, O., Neduvelil, J., Wang, X., and Sansom, M., HOLE: A Program for the Analysis of the Pore Dimensions of Ion Channel Structural Models, J. Mol. Graphics, 1996, vol. 14, pp. 354–360.

    Article  CAS  Google Scholar 

  9. Duan, Y., Wu, C., Chowdhury, S., Lee, M., Xiong, G., Zhang, W., Yang, R., Cieplak, P., Luo, R., Lee, T., Caldwell, J., Wang, J., and Kollman, P., A PointCharge Force Field for Molecular Mechanics Simulations of Proteins Based on Condensed-Phase Quantum Mechanical Calculations, J. Comput. Chem., 2003, vol. 24, pp. 1999–2012.

    Article  PubMed  CAS  Google Scholar 

  10. Miloshevsky, G. and Jordan, P., Conformational Changes in the Selectivity Filter of the Open-State KcsA Channel: An Energy Minimization Study, Biophys. J., 2008, vol. 95, pp. 3239–3251.

    Article  PubMed  CAS  Google Scholar 

  11. Berger, O., Edholm, O., and Jahnig, F., Molecular Dynamics Simulations of a Fluid Bilayer of Dipalmitoylphosphatidylcholine at Full Hydration, Constant Pressure, and Constant Temperature, Biophys. J., 1997, vol. 72, pp. 2002–2013.

    Article  PubMed  CAS  Google Scholar 

  12. Wolf, M.G., Hoefling, M., Aponte-Santamaia, C., Grubmuller, H., and Groenhof, G., G-membed: Efficient Insertion of a Membrane Protein into an Equilibrated Lipid Bilayer with Minimal Perturbation, J. Comput. Chem., 2010, vol. 31, pp. 2169–2174.

    Article  PubMed  CAS  Google Scholar 

  13. Case, D., Gohlke, K., Luo, R., Merz, K., Onufriev, A., Simmerling, C., and Woods, R., The Amber Biomolecular Simulation Programs, J. Comput. Chem., 2005, vol. 26, pp. 1668–1688.

    Article  PubMed  CAS  Google Scholar 

  14. Phillips, J., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R., Kale, L., and Schulten, K., Scalable Molecular Dynamics with NAMD, J. Comput. Chem., 2005, vol. 26, pp. 1781–1802.

    Article  PubMed  CAS  Google Scholar 

  15. Karlova, M.G., Piscshalnikova, A.V., Ramonova, A.A., Moisenovich, M.M., Sokolova, O.S., and Shaitan, K.V., In vitro Fluorescence Assay to Study the Folding of Kv Ion Channels, Biophysics (Moscow), 2011, vol. 56, no. 2, pp. 272–279.

    CAS  Google Scholar 

  16. Long, S.B., Campbell, E.B., and Mackinnon, R., Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel, Science, 2005, vol. 309, pp. 897–903.

    Article  PubMed  CAS  Google Scholar 

  17. Krezel, A.M., Hidalgo, P., MacKinnon, R., and Wagner, G., Solution Structure of the Potassium Channel Inhibitor Agitoxin 2: Caliper for Probing Channel Geometry, Protein Sci., 1995, vol. 4, pp. 1478–1489.

    Article  PubMed  CAS  Google Scholar 

  18. Maestro, version 9.5, Schrödinger L.L.C., New York, 2007. http://www.schrodinger.corr

  19. Eriksson, M.A. and Roux, B., Modeling the Structure of Agitoxin in Complex with the Shaker K+ Channel: A Computational Approach Based on Experimental Distance Restraints Extracted from Thermodynamic Mutant Cycles, Biophys. J., 2002, vol. 83, no. 5, pp. 2595–609.

    Article  PubMed  CAS  Google Scholar 

  20. Tieleman, D.P., Sansom, M.S.P., and Berendsen, H.J., Alamethicin Helices in a Bilayer and in Solution: Molecular Dynamics Simulations, Biophys. J., 1999, vol. 76, p. 40.

    Article  PubMed  CAS  Google Scholar 

  21. Humphrey, W., Dalke, A., and Schulten, K., VMD: Visual Molecular Dynamics, J. Mol. Graphics, 1996, vol. 14, pp. 33–38.

    Article  CAS  Google Scholar 

  22. Dolinsky, T.J., Czodrowski, P., Li, H., Nielsen, J.E., Jensen, J.H., Klebe, G., and Baker, N.A., PDB2PQR: Expanding and Upgrading Automated Preparation of Biomolecular Structures for Molecular Simulations, Nucleic Acids Res., 2007, vol. 35, pp. W522–W525.

    Article  PubMed  Google Scholar 

  23. Chakrapani, S., Cordero-Morales, J., and Perozo, E., A Quantitative Description of KcsA Gating II: Single-Channel Currents, J. Gen. Physiol., 2007, vol. 130, pp. 479–496.

    Article  PubMed  CAS  Google Scholar 

  24. LeMasurier, M., Hegittbotham, L., and Miller, C., Kcsa. It’s a Potassium Channel, J. Gen. Physiol., 2001, vol. 118, pp. 303–314.

    Article  PubMed  CAS  Google Scholar 

  25. Grottesi, A. and Sansom, M.S., Molecular Dynamics Simulations of a K+ Channel Blocker: Tcl Toxin from Tityus cambridgei, FEBS Lett., 2003, vol. 535, nos. 1–3, pp. 29–33.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, Moscow State University, Moscow, 119991, Russia

    K. V. Shaitan, O. S. Sokolova, A. K. Shaitan, M. A. Kasimova, V. N. Novoseletskii & M. P. Kirpichnikov

Authors
  1. K. V. Shaitan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. S. Sokolova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. K. Shaitan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. A. Kasimova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. N. Novoseletskii
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. P. Kirpichnikov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. V. Shaitan.

Additional information

Original Russian Text © K.V. Shaitan, O.S. Sokolova, A.K. Shaitan, M.A. Kasimova, V.N. Novoseletskii, M.P. Kirpichnikov, 2013, published in Vestnik Moskovskogo Universiteta. Biologiya, 2013, No. 1, pp. 17–23.

About this article

Cite this article

Shaitan, K.V., Sokolova, O.S., Shaitan, A.K. et al. Influence of interionic interactions on functional state and blocker binding of voltage-gated potassium channels. Moscow Univ. Biol.Sci. Bull. 68, 8–14 (2013). https://doi.org/10.3103/S0096392513010057

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0096392513010057

Keywords

Search

Navigation