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A molecular level prototype for mechanoelectrical transducer in mammalian hair cells

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Abstract

The mechanoelectrical transducer (MET) is a crucial component of mammalian auditory system. The gating mechanism of the MET channel remains a puzzling issue, though there are many speculations, due to the lack of essential molecular building blocks. To understand the working principle of mammalian MET, we propose a molecular level prototype which constitutes a charged blocker, a realistic ion channel and its surrounding membrane. To validate the proposed prototype, we make use of a well-established ion channel theory, the Poisson–Nernst–Planck equations, for three-dimensional (3D) numerical simulations. A wide variety of model parameters, including bulk ion concentration, applied external voltage, blocker charge and blocker displacement, are explored to understand the basic function of the proposed MET prototype. We show that our prototype prediction of channel open probability in response to blocker relative displacement is in remarkable accordance with experimental observation of rat cochlea outer hair cells. Our results appear to suggest that tip links which connect hair bundles gate MET channels.

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References

  • Beurg, M., Nam, J.H., Crawford, A., Fettiplace, R. (2008). The actions of calcium on hair bundle mechanics in mammalian cochlear hair cells. Biophysical Journal, 94(7), 2639–2653.

    Article  PubMed  CAS  Google Scholar 

  • Beurg, M., Fettiplace, R., Nam, J.H., Ricci, A.J. (2009). Localization of inner hair cell mechanotransducer channels using high-speed calcium imaging. Nature Neuroscience, 12(5), 553–558.

    Article  PubMed  CAS  Google Scholar 

  • Beurg, M., Nam, J.H., Chen, Q., Fettiplace, R. (2010). Calcium balance and mechanotransduction in rat cochlear hair cells. Journal of Neurophysiology, 104(1), 18–34.

    Article  PubMed  CAS  Google Scholar 

  • Borisyuk, A. (2005). Physiology and mathematical modeling of the auditory system. Tutorials in Mathematical Biosciences I, 1860, 107–168.

    Google Scholar 

  • Chen, D., & Eisenberg, R. (1993). Charges, currents, and potentials in ionic channels of one conformation. Biophysical Journal, 64(5), 1405–1421.

    Article  PubMed  CAS  Google Scholar 

  • Chen, D., & Wei, G.W. (2012). Quantum dynamics in continuum for proton transportgeneralized correlation. The Journal of Chemical Physics, 136, 134109.

    Article  PubMed  Google Scholar 

  • Coalson, R.D., & Kurnikova, M.G. (2005). Poisson–Nernst–Planck theory approach to the calculation of current through biological ion channels. IEEE Transactions on NanoBioscience, 4(1), 81–93.

    Article  PubMed  Google Scholar 

  • Denk, W., Holt, J.R., Shepherd, G.M.G., Coreytt, D.P. (1995). Calcium imaging of single stereocilia in hair cells: localization of transduction channels at both ends of tip links. Neuron, 15(6), 1311–1321.

    Article  PubMed  CAS  Google Scholar 

  • Dolinsky, T., Nielsen, J., McCammon, J., Baker, N. (2004). Pdb2pqr: an automated pipeline for the setup of Poisson–Boltzmann electrostatics calculations. Nucleic Acids Research, 32(suppl 2), W665–W667.

    Article  PubMed  CAS  Google Scholar 

  • Dolinsky, T., Czodrowski, P., Li, H., Nielsen, J., Jensen, J., Klebe, G., Baker, N. (2007). Pdb2pqr: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Research, 35(suppl 2), W522–W525.

    Article  PubMed  Google Scholar 

  • Eisenberg, B.S., Hyon, Y.K., Liu, C. (2010). Energy variational analysis of ions in water and channels: field theory for primitive models of complex ionic fluids. Journal of Chemical Physics, 133, 104104.

    Article  PubMed  Google Scholar 

  • Farris, H.E., LeBlanc, C.L., Goswami, J., Ricci, A.J. (2004). Probing the pore of the auditory hair cell mechanotransducer channel in turtle. The Journal of physiology, 558(3), 769–792.

    Article  PubMed  CAS  Google Scholar 

  • Fettiplace, R. (2009). Defining features of the hair cell mechanoelectrical transducer channel. Pflügers Archiv European Journal of Physiology, 458(6), 1115–1123.

    Article  PubMed  CAS  Google Scholar 

  • Fettiplace, R., & Hackney, C.M. (2006). The sensory and motor roles of auditory hair cells. Nature Reviews Neuroscience, 7(1), 19–29.

    Article  PubMed  CAS  Google Scholar 

  • Geng, W., Yu, S., Wei, G. (2007). Treatment of charge singularities in implicit solvent models. The Journal of Chemical Physics, 127, 114106.

    Article  PubMed  Google Scholar 

  • Gillespie, P.G., & Müller, U. (2009). Mechanotransduction by hair cells: models, molecules, and mechanisms. Cell, 139(1), 33–44.

    Article  PubMed  CAS  Google Scholar 

  • Hacker, M.P., Messer, W.S., Bachmann, K.A. (2009). Pharmacology: principles and practice. Academic Press.

  • Hodgkin, A.L., & Huxley, A.F. (1952). The dual effect of membrane potential on sodium conductance in the giant axon of Loligo. The Journal of Physiology, 116(4), 497–506.

    PubMed  CAS  Google Scholar 

  • Hollerbach, U., Chen, D.P., Eisenberg, R.S. (2001). Two- and three-dimensional Poisson–Nernst–Planck simulations of current flow through gramicidin A. Journal of Scientific Computing, 16(4), 373–409.

    Article  Google Scholar 

  • Howard, J., & Hudspeth, A.J. (1988). Compliance of the hair bundle associated with gating of mechanoelectrical transduction channels in the bullfrog’s saccular hair cell. Neuron, 1(3), 189–199.

    Article  PubMed  CAS  Google Scholar 

  • Jaramillo, F., & Hudspeth, A.J. (1991). Localization of the hair cell’s transduction channels at the hair bundle’s top by iontophoretic application of a channel blocker. Neuron, 7(3), 409–420.

    Article  PubMed  CAS  Google Scholar 

  • Jordan, P.C. (2005). Fifty years of progress in ion channel research. IEEE Transactions on NanoBioscience, 4(1), 3–9.

    Article  PubMed  Google Scholar 

  • Jung, Y.W., Lu, B., Mascagni, M. (2009). A computational study of ion conductance in the kcsa k channel using a Nernst–Planck model with explicit resident ions. The Journal of Chemical Physics, 131, 215101.

    Article  PubMed  Google Scholar 

  • Kazmierczak, P., & Müller, U. (2012). Sensing sound: molecules that orchestrate mechanotransduction by hair cells. Trends in Neurosciences, 35(4), 220–229.

    Article  PubMed  CAS  Google Scholar 

  • Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E.M., Milligan, R.A., Müller, U., Kachar, B. (2007). Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells. Nature, 449(7158), 87–91.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy, H.J., Evans, M.G., Crawford, A.C., Fettiplace, R. (2003). Fast adaptation of mechanoelectrical transducer channels in mammalian cochlear hair cells. Nature Neuroscience, 6(8), 832–836.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy, H.J., Crawford, A.C., Fettiplace, R. (2005). Force generation by mammalian hair bundles supports a role in cochlear amplification. Nature, 433(7028), 880–883.

    Article  PubMed  CAS  Google Scholar 

  • Lu, B., & Zhou, Y. (2011). Poisson–Nernst–Planck equations for simulating biomolecular diffusion-reaction processes ii: size effects on ionic distributions and diffusion-reaction rates. Biophysical Journal, 100(10), 2475–2485.

    Article  PubMed  CAS  Google Scholar 

  • Lu, B., Zhou, Y., Huber, G., Bond, S., Holst, M., McCammon, J. (2007). Electrodiffusion: a continuum modeling framework for biomolecular systems with realistic spatiotemporal resolution. The Journal of Chemical Physics, 127, 135102.

    Article  PubMed  Google Scholar 

  • MacKerell, A., Bashford, D., Bellott, M., Dunbrack, R., Evanseck, J., Field, M., Fischer, S., Gao, J., Guo, H., Ha, S., et al. (1998). All-atom empirical potential for molecular modeling and dynamics studies of proteins. The Journal of Physical Chemistry B, 102(18), 3586–3616.

    Article  CAS  Google Scholar 

  • Peng, A.W., Salles, F.T., Pan, B., Ricci, A.J. (2011). Integrating the biophysical and molecular mechanisms of auditory hair cell mechanotransduction. Nature Communications, 2, 523.

    Article  PubMed  Google Scholar 

  • Ricci, A.J., Crawford, A.C., Fettiplace, R. (2003). Tonotopic variation in the conductance of the hair cell mechanotransducer channel. Neuron, 40(5), 983–990.

    Article  PubMed  CAS  Google Scholar 

  • Ricci, A.J., Kachar, B., Gale, J., Van Netten, S.M. (2006). Mechano-electrical transduction: new insights into old ideas. Journal of Membrane Biology, 209(2), 71–88.

    PubMed  CAS  Google Scholar 

  • Roux, B., Allen, T., Berneche, S., Im, W. (2004). Theoretical and computational models of biological ion channels. Quarterly Reviews of Biophysics, 37(01), 15–103.

    Article  PubMed  CAS  Google Scholar 

  • Sanner, M., Olson, A., Spehner, J. (1996). Reduced surface: an efficient way to compute molecular surfaces. Biopolymers, 38(3), 305–320.

    Article  PubMed  CAS  Google Scholar 

  • Schwander, M., Kachar, B., Müller, U. (2010). Review series: the cell biology of hearing. The Journal of Cell Biology, 190(1), 9–20.

    Article  PubMed  CAS  Google Scholar 

  • Wei, G.W., Zheng, Q., Chen, Z., Xia, K. (2012). Variational multiscale models for charge transport. SIAM Review, 54(4), 699–754.

    Article  PubMed  Google Scholar 

  • Yu, S.N., & Wei, G.W. (2007). Three-dimensional matched interface and boundary (MIB) method for treating geometric singularities. Journal of Computational Physics, 227(1), 602–632.

    Article  Google Scholar 

  • Zhao, S., & Wei, G.W. (2004). High-order FDTD methods via derivative matching for Maxwell’s equations with material interfaces. Journal of Computational Physics, 200(1), 60–103.

    Article  Google Scholar 

  • Zheng, Q., & Wei, G.W. (2011). Poisson–Boltzmann–Nernst–Planck model. The Journal of Chemical Physics, 134, 194101.

    Article  PubMed  Google Scholar 

  • Zheng, Q., Chen, D., Wei, G.W. (2011). Second-order Poisson–Nernst–Planck solver for ion transport. Journal of Computational Physics, 230, 5239–5262.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, Y.C., Zhao, S., Feig, M., Wei, G.W. (2006). High order matched interface and boundary method for elliptic equations with discontinuous coefficients and singular sources. Journal of Computational Physics, 213(1), 1–30.

    Article  Google Scholar 

Download references

Acknowledgments

JP thanks Ms Qiong Zheng and Dr Kelin Xia for technical assistance. This work was supported in part by NSF grants CCF-0936830, DMS-1160352 and NIH grant R01GM-090208.

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Authors and Affiliations

  1. Department of Mathematics, Michigan State University, East Lansing, MI, 48824, USA

    Jinkyoung Park & Guo-Wei Wei

  2. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA

    Guo-Wei Wei

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  1. Jinkyoung Park
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  2. Guo-Wei Wei
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Correspondence to Guo-Wei Wei.

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Park, J., Wei, GW. A molecular level prototype for mechanoelectrical transducer in mammalian hair cells. J Comput Neurosci 35, 231–241 (2013). https://doi.org/10.1007/s10827-013-0450-z

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  • DOI: https://doi.org/10.1007/s10827-013-0450-z

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