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Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes


Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.

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Figure 1: Principle and experimental set-up of functional electrochemical stimulation with in situ ion concentration modulation through ISMs.
Figure 2: Operation modes of electrochemical stimulation with modulation of the local ion concentration adjacent to a nerve.
Figure 3: Comparison of excitability without and with modulating Ca2+ ion concentration.
Figure 4: Characterization of the electrochemical stimulation device under various parametric conditions.
Figure 5: Nerve-conduction-block experiment with a microfabricated ISM device.


  1. Katz, B. Society of Experimental Biology Symposia 4. Structural Aspects of Cell Physiology 16–38 (Cambrige Univ. Press, 1952).

    Google Scholar 

  2. Hodgkin, A. L. & Huxley, A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117, 500–544 (1952).

    Article  CAS  Google Scholar 

  3. Kandel, E. R., Schwartz, J. H. & Jessell, T. M. Principles of Neural Science (McGraw-Hill, 2000).

    Google Scholar 

  4. Brink, F. The role of calcium ions in neural processes. Pharmacol. Rev. 6, 243–298 (1954).

    CAS  Google Scholar 

  5. Brink, F., Bronk, D. W. & Larrabee, M. G. Chemical excitation of nerve. Ann. New York Acad. Sci. 47, 457–485 (1946).

    Article  CAS  Google Scholar 

  6. Santini, J. T., Cima, M. J. & Langer, R. A controlled-release microchip. Nature 397, 335–338 (1999).

    Article  CAS  Google Scholar 

  7. Chen, J. & Wise, K. D. Solid-State Sensor and Actuator Workshop 256–259 (Cleveland Heights, 1994).

    Google Scholar 

  8. Ammann, D., Buehrer, T., Schefer, U., Mueller, M. & Simon, W. Intracellular neutral carrier-based Ca2+ microelectrode with subnanomolar detection limit. Pfluegers Arch. 409, 223–228 (1987).

    Article  CAS  Google Scholar 

  9. Baudet, S., Hove-Madsen, L. & Bers, D. M. in Methods in Cell Biology Vol. 40 (ed. Nuccitelli, R.) Ch. 4 (American Society for Cell Biology, Academic, 1994).

    Google Scholar 

  10. Bostock, H., Cikurel, K. & Burke, D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve 21, 137–158 (1998).

    Article  CAS  Google Scholar 

  11. Bostock, H. & Grafe, P. Acitivity-dependent excitability changes in normal and demyelinated rat spinal root axons. J. Physiol. 365, 239–257 (1985).

    Article  CAS  Google Scholar 

  12. Ask, P., Levitan, H., Robinson, P. J. & Rapoport, S. I. Peripheral nerve as an osmometer: Role of the perineurium in frog sciatic nerve. Am. J. Physiol. 244, C75–C81 (1983).

    Article  CAS  Google Scholar 

  13. Weerasuriya, A., Spangler, R. A., Rapoport, S. I. & Taylor, R. E. AC impedance of the perineurium of the frog sciatic nerve. Biophys. J. 46, 167–174 (1984).

    Article  CAS  Google Scholar 

  14. Bradbury, M. W. & Crowder, J. Compartments and barriers in the sciatic nerve of the rabbit. Brain Res. 103, 515–526 (1976).

    Article  CAS  Google Scholar 

  15. Abbott, N. J., Mitchell, G., Ward, K. J., Abdullah, F. & Smith, I. C. An electrophysiological method for measuring the potassium permeability of the nerve perineurium. Brain Res. 776, 204–213 (1997).

    Article  CAS  Google Scholar 

  16. Petruska, J. C., Hubscher, C. H. & Johnson, R. D. Anodally focused polarization of peripheral nerve allows discrimination of myelinated and unmyelinated fiber input to brainstem nuclei. Exp. Brain Res. 121, 379–390 (1998).

    Article  CAS  Google Scholar 

  17. Manfredi, M. Differential block of conduction of large fibers in peripheral nerve by direct current. Arch. Ital. Biol. 108, 52–71 (1970).

    CAS  Google Scholar 

  18. Bhadra, N. & Kilgore, K. L. Direct current electrical conduction block of peripheral nerve. IEEE Trans. Neural Syst. Rehabil. Eng. 12, 313–324 (2004).

    Article  Google Scholar 

  19. Tanner, J. A. Reversible blocking of nerve conduction by alternating-current excitation. Nature 195, 712–713 (1962).

    Article  CAS  Google Scholar 

  20. Kilgore, K. L. & Bhadra, N. Nerve conduction block utilising high-frequency alternating current. Med. Biol. Eng. Comput. 42, 394–406 (2004).

    Article  CAS  Google Scholar 

  21. Bhadra, N. & Kilgore, K. L. High-frequency nerve conduction block. Conf. Proc. IEEE Eng. Med. Biol. Soc. 7, 4729–4732 (2004).

    CAS  Google Scholar 

  22. Isaksson, J. et al. Electronic control of Ca2+ signalling in neuronal cells using an organic electronic ion pump. Nature Mater. 6, 673–679 (2007).

    Article  CAS  Google Scholar 

  23. Olsson, Y. & Reese, T. S. Permeability of vasa nervorum and perineurium in mouse sciatic nerve studied by fluorescence and electron microscopy. J. Neuropathol. Exp. Neurol. 30, 105–119 (1971).

    Article  CAS  Google Scholar 

  24. Waggener, J. D., Bunn, S. M. & Beggs, J. The diffusion of ferritin within the peripheral nerve sheath, an electron microscopy study. J. Neuropathol. Exp. Neurol. 24, 430–443 (1965).

    Article  Google Scholar 

  25. Feng, T. P. & Liu, Y. M. The connective tissue sheath of the nerve as effective diffusion barrier. J. Cell. Physiol. 34, 1–16 (1949).

    Article  CAS  Google Scholar 

  26. Krnjevic, K. The distribution of Na and K in cat nerves. J. Physiol. 128, 473–488 (1955).

    Article  CAS  Google Scholar 

  27. Seneviratne, K. N. & Weerasuriya, A. Nodal gap substance in diabetic nerve. J. Neurol. Neurosurg. Psychiatry 37, 502–513 (1974).

    Article  CAS  Google Scholar 

  28. Weerasuriya, A. Permeability of endoneurial capillaries to K, Na and Cl and its relation to peripheral nerve excitability. Brain Res. 419, 188–196 (1987).

    Article  CAS  Google Scholar 

  29. Prodanov, D., Marani, E. & Holsheimer, J. Functional eletric stimulation for sensory and motor functions: Progress and problems. Biomed. Rev. 14, 23–50 (2003).

    Article  Google Scholar 

  30. Mortimer, J. in Handbook of Physiology—the Nervous System II (eds Brookshart, J. M. & Mountcastle, V. B.) (American Physiology Society, 1981).

    Google Scholar 

  31. Kim, D. H. et al. Stretchable and foldable silicon integrated circuits. Science 320, 507–511 (2008).

    Article  CAS  Google Scholar 

  32. Guenat, O. T. et al. Microfabrication and characterization of an ion-selective microelectrode array platform. Sens. Actuat. B 105, 65–73 (2005).

    Article  CAS  Google Scholar 

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This work was conducted with support from a Massachusetts Institute of Technology faculty discretionary research fund, a Harvard Catalyst Grant from the Harvard Clinical and Translational Science Center (National Institutes of Health Award UL1 RR 025758) and financial contributions from Harvard University and its affiliated academic health-care centres.

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Y-A.S. carried out fabrication of ion-selective electrodes and membranes, experimental work and confocal imaging. R.M., A.N.R., A.M.S.I., D.M. and A.T. conducted experimental work and data analysis. J.H. and S.J.L. carried out project planning. A.N.R., Y-A.S., S.J.L. and J.H. wrote the manuscript.

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Correspondence to Jongyoon Han or Samuel J. Lin.

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The authors have applied for a patent based on the technique described in this paper.

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Song, YA., Melik, R., Rabie, A. et al. Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes. Nature Mater 10, 980–986 (2011).

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