Electrodiffusion phenomena in neuroscience: a neglected companion

Key Points

  • Classical principles of electrophysiology become inaccurate on the nanoscale because some of the underlying assumptions do not hold at such small distances.

  • The molecular composition of the cell membrane influences electric fields that occur near the membrane surface and controls the activity of voltage-sensitive membrane receptors or channels. Classical patch-clamp recording methods are usually unable to detect such effects.

  • Neuronal activity can lead to rapid redistributions of electrolyte ions in narrow spaces such as synaptic clefts or dendritic spines. The resulting dynamics of local voltage and current will differ from that predicted by the classical theories.

  • Ionic currents may exert electro-osmotic forces acting on local membrane proteins, thus prompting their lateral movement. The resulting rearrangement may alter individual or cooperative protein properties, thus affecting local cellular function.

  • Large immobile ions can perturb local electrolyte electroneutrality inside or outside cells but are unlikely to influence bulk electrolyte properties in the surrounding medium.


The emerging technological revolution in genetically encoded molecular sensors and super-resolution imaging provides neuroscientists with a pass to the real-time nano-world. On this small scale, however, classical principles of electrophysiology do not always apply. This is in large part because the nanoscopic heterogeneities in ionic concentrations and the local electric fields associated with individual ions and their movement can no longer be ignored. Here, we review basic principles of molecular electrodiffusion in the cellular environment of organized brain tissue. We argue that accurate interpretation of physiological observations on the nanoscale requires a better understanding of the underlying electrodiffusion phenomena.

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Figure 1: Electric charges and their fields in brain tissue: basic principles and two common deviations from common electrophysiological postulates.
Figure 2: Patch-clamp measurements of membrane potential: first principles.
Figure 3: The effect of membrane-impermeable intracellular anions on transmembrane ion exchange.
Figure 4: Possible physiological implications of electrodiffusion and electro-osmosis in the synaptic cleft.


  1. 1

    Triller, A. & Choquet, D. New concepts in synaptic biology derived from single-molecule imaging. Neuron 59, 359–374 (2008).

  2. 2

    Novak, P. et al. Nanoscale-targeted patch-clamp recordings of functional presynaptic ion channels. Neuron 79, 1067–1077 (2013).

  3. 3

    Hochbaum, D. R. et al. All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat. Methods 11, 825–833 (2014).

  4. 4

    Tonnesen, J., Katona, G., Rozsa, B. & Nagerl, U. V. Spine neck plasticity regulates compartmentalization of synapses. Nat. Neurosci. 17, 678–685 (2014).

  5. 5

    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).

  6. 6

    Buzsaki, G., Anastassiou, C. A. & Koch, C. The origin of extracellular fields and currents—EEG, ECoG, LFP and spikes. Nat. Rev. Neurosci. 13, 407–420 (2012).

  7. 7

    Pods, J., Schonke, J. & Bastian, P. Electrodiffusion models of neurons and extracellular space using the Poisson-Nernst-Planck equations—numerical simulation of the intra- and extracellular potential for an axon model. Biophys. J. 105, 242–254 (2013).

  8. 8

    Mori, Y. & Peskin, C. S. A numerical method for cellular electrophysiology based on the electrodiffusion equations with internal boundary conditions at membranes. Commun. Appl. Math. Computat. Sci. 4, 85–134 (2009).

  9. 9

    Lopreore, C. L. et al. Computational modeling of three-dimensional electrodiffusion in biological systems: application to the node of Ranvier. Biophys. J. 95, 2624–2635 (2008).

  10. 10

    Savtchenko, L. P., Korogod, S. M. & Rusakov, D. A. Electrodiffusion of synaptic receptors: a mechanism to modify synaptic efficacy? Synapse 35, 26–38 (2000).

  11. 11

    Zhang, L. I. & Poo, M. M. Electrical activity and development of neural circuits. Nat. Neurosci. 4, 1207–1214 (2001).

  12. 12

    Eccles, J. C. & Jaeger, J. C. The relationship between the mode of operation and the dimensions of the junctional regions at synapses and motor end-organs. Proc. R. Soc. B 148, 38–56 (1958). This study is a pioneering theoretical work predicting a substantial effect of electric fields on ion currents in small spaces such as the synaptic cleft.

  13. 13

    Savtchenko, L. P., Antropov, S. N. & Korogod, S. M. Effect of voltage drop within the synaptic cleft on the current and voltage generated at a single synapse. Biophys. J. 78, 1119–1125 (2000).

  14. 14

    Savtchenko, L. P. & Rusakov, D. A. The optimal height of the synaptic cleft. Proc. Natl Acad. Sci. USA 104, 1823–1828 (2007).

  15. 15

    Poo, M. M. Insitu electrophoresis of membrane-components. Annu. Rev. Biophys. Bio 10, 245–276 (1981).

  16. 16

    Orida, N. & Poo, M. M. Electrophoretic movement and localization of acetylcholine receptors in embryonic muscle-cell membrane. Nature 275, 31–35 (1978).

  17. 17

    Eisenberg, B. Interacting ions in biophysics: real is not ideal. Biophys. J. 104, 1849–1866 (2013).

  18. 18

    Eisenberg, B. Ionic interactions are everywhere. Physiol. (Bethesda) 28, 28–38 (2013).

  19. 19

    Holcman, D. & Yuste, R. The new nanophysiology: regulation of ionic flow in neuronal subcompartments. Nat. Rev. Neurosci. 16, 685–692 (2015).

  20. 20

    Torriero, A. A. J. (ed) Electrochemistry in Ionic Liquids: Volume 1: Fundamentals (Springer, 2015).

  21. 21

    Pods, J. A. Comparison of computational models for the extracellular potential of neurons. arXiv http://dx.doi.org/10.3233/JIN-170009 (2015).

  22. 22

    Luo, Z. X., Xing, Y. Z., Ling, Y. C., Kleinhammes, A. & Wu, Y. Electroneutrality breakdown and specific ion effects in nanoconfined aqueous electrolytes observed by NMR. Nat. Commun. 6, 6358 (2015).

  23. 23

    DeFelice, L. J. Electrical Properties of Cells: Patch Clamp for Biologists (Plenum Press, 1997).

  24. 24

    Steinberg, J. S. & Mittal, S. Electrophysiology: the Basics 2nd edn (Wolters Kluwer Heath, 2017).

  25. 25

    Macdonald, J. R. A new model for the debye dispersion equations. Phys. Rev. 91, 412–412 (1953).

  26. 26

    Bagotsky, V. S. (ed.) Fundamentals of Electrochemistry 2nd edn (John Wiley & Sons, 2006).

  27. 27

    Perram, J. W. & Stiles, P. J. On the nature of liquid junction and membrane potentials. Phys. Chem. Chem. Phys. 8, 4200–4213 (2006).

  28. 28

    Plonsey, R., Henriquez, C. & Trayanova, N. Extracellular (volume conductor) effect on adjoining cardiac muscle electrophysiology. Med. Biol. Eng. Comput. 26, 126–129 (1988).

  29. 29

    Clark, J. & Plonsey, R. The extracellular potential field of the single active nerve fiber in a volume conductor. Biophys. J. 8, 842–864 (1968). This study provided an important theoretical introduction to the use of mathematical formalism in calculating extracellular electric fields.

  30. 30

    Thorne, R. G. & Nicholson, C. In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space. Proc. Natl Acad. Sci. USA 103, 5567–5572 (2006).

  31. 31

    Sykova, E. & Nicholson, C. Diffusion in brain extracellular space. Physiol. Rev. 88, 1277–1340 (2008).

  32. 32

    Hrabetova, S., Hrabe, J. & Nicholson, C. Dead-space microdomains hinder extracellular diffusion in rat neocortex during ischemia. J. Neurosci. 23, 8351–8359 (2003).

  33. 33

    Kinney, J. P. et al. Extracellular sheets and tunnels modulate glutamate diffusion in hippocampal neuropil. J. Comp. Neurol. 521, 448–464 (2013).

  34. 34

    Zheng, K. et al. Nanoscale diffusion in the synaptic cleft and beyond measured with time-resolved fluorescence anisotropy imaging. Sci. Rep. 7, 42022 (2017).

  35. 35

    Rusakov, D. A. & Kullmann, D. M. Geometric and viscous components of the tortuosity of the extracellular space in the brain. Proc. Natl Acad. Sci. USA 95, 8975–8980 (1998).

  36. 36

    Hrabetova, S., Masri, D., Tao, L., Xiao, F. & Nicholson, C. Calcium diffusion enhanced after cleavage of negatively charged components of brain extracellular matrix by chondroitinase ABC. J. Physiol. 587, 4029–4049 (2009).

  37. 37

    Miranda, P. C., Hallett, M. & Basser, P. J. The electric field induced in the brain by magnetic stimulation: a 3D finite-element analysis of the effect of tissue heterogeneity and anisotropy. IEEE Trans. Biomed. Eng. 50, 1074–1085 (2003).

  38. 38

    Bazhenov, M., Lonjers, P., Skorheim, S., Bedard, C. & Dstexhe, A. Non-homogeneous extracellular resistivity affects the current-source density profiles of up-down state oscillations. Philos. Trans. A Math. Phys. Eng. Sci. 369, 3802–3819 (2011).

  39. 39

    Rusakov, D. A. Disentangling calcium-driven astrocyte physiology. Nat. Rev. Neurosci. 16, 226–233 (2015).

  40. 40

    Gleixner, R. & Fromherz, P. The extracellular electrical resistivity in cell adhesion. Biophys. J. 90, 2600–2611 (2006).

  41. 41

    Rudy, Y. & Plonsey, R. Volume conductor and geometrical effects on body-surface and epicardial potentials.1. Theory. Phys. Med. Biol. 25, 978–978 (1980).

  42. 42

    Hallez, H. et al. Review on solving the forward problem in EEG source analysis. J. Neuroeng. Rehabil. 4, 46 (2007).

  43. 43

    McLaughlin, S. The electrostatic properties of membranes. Annu. Rev. Biophys. Biophys. Chem. 18, 113–136 (1989).

  44. 44

    Greathouse, J. A., Feller, S. E. & Mcquarrie, D. A. The modified Gouy-Chapman theory - comparisons between electrical double-layer models of clay swelling. Langmuir 10, 2125–2130 (1994).

  45. 45

    Zheng, K., Scimemi, A. & Rusakov, D. A. Receptor actions of synaptically released glutamate: the role of transporters on the scale from nanometers to microns. Biophys. J. 95, 4584–4596 (2008).

  46. 46

    Nadler, B., Naeh, T. & Schuss, Z. Connecting a discrete ionic simulation to a continuum. SIAM J. Appl. Math. 63, 850–873 (2003).

  47. 47

    Sylantyev, S., Savtchenko, L. P., Ermolyuk, Y., Michaluk, P. & Rusakov, D. A. Spike-driven glutamate electrodiffusion triggers synaptic potentiation via a Homer-dependent mGluR-NMDAR link. Neuron 77, 528–541 (2013).

  48. 48

    Guerrier, C. & Holcman, D. Hybrid Markov-mass action law model for cell activation by rare binding events: application to calcium induced vesicular release at neuronal synapses. Sci. Rep. 6, 35506 (2016).

  49. 49

    Marhl, M., Brumen, M., Glaser, R. & Heinrich, R. Diffusion layer caused by local ionic transmembrane fluxes. Pflugers Arch. 431, R259–R260 (1996).

  50. 50

    McLaughlin, S. G., Szabo, G. & Eisenman, G. Divalent ions and the surface potential of charged phospholipid membranes. J. Gen. Physiol. 58, 667–687 (1971).

  51. 51

    Ward, K. R., Dickinson, E. J. F. & Compton, R. G. How far do membrane potentials extend in space beyond the membrane itself? Int. J. Electrochem. Sci. 5, 1527–1534 (2010).

  52. 52

    Stuart, G., Schiller, J. & Sakmann, B. Action potential initiation and propagation in rat neocortical pyramidal neurons. J. Physiol.-Lond. 505, 617–632 (1997).

  53. 53

    Bezanilla, F. The voltage sensor in voltage-dependent ion channels. Physiol. Rev. 80, 555–592 (2000).

  54. 54

    Catterall, W. A. Ion channel voltage sensors: structure, function, and pathophysiology. Neuron 67, 915–928 (2010).

  55. 55

    Neher, E. Correction for liquid junction potentials in patch clamp experiments. Method Enzymol. 207, 123–131 (1992).

  56. 56

    von J. J. Lingane . Electroanalytical Chemistry (Interscience Publishers, 1958).

  57. 57

    Dickinson, E. J., Freitag, L. & Compton, R. G. Dynamic theory of liquid junction potentials. J. Phys. Chem. B 114, 187–197 (2010).

  58. 58

    Barton, P. G. The influence of surface charge density of phosphatides on the binding of some cations. J. Biol. Chem. 243, 3884–3890 (1968).

  59. 59

    Gurtovenko, A. A. & Vattulainen, I. Membrane potential and electrostatics of phospholipid bilayers with asymmetric transmembrane distribution of anionic lipids. J. Phys. Chem. B 112, 4629–4634 (2008).

  60. 60

    van Meer, G., Voelker, D. R. & Feigenson, G. W. Membrane lipids: where they are and how they behave. Nat. Rev. Mol. Cell Biol. 9, 112–124 (2008).

  61. 61

    Isaev, D. et al. Surface charge impact in low-magnesium model of seizure in rat hippocampus. J. Neurophysiol. 107, 417–423 (2012).

  62. 62

    Rusakov, D. A. & Fine, A. Extracellular Ca2+ depletion contributes to fast activity-dependent modulation of synaptic transmission in the brain. Neuron 37, 287–297 (2003).

  63. 63

    Annunziato, L., Pignataro, G. & Di Renzo, G. F. Pharmacology of brain Na+/Ca2+ exchanger: from molecular biology to therapeutic perspectives. Pharmacol. Rev. 56, 633–654 (2004).

  64. 64

    Hahin, R. & Campbell, D. T. Simple shifts in the voltage dependence of sodium channel gating caused by divalent cations. J. Gen. Physiol. 82, 785–805 (1983).

  65. 65

    Hille, B., Woodhull, A. M. & Shapiro, B. I. Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH. Phil. Trans. R. Soc. Lond. B 270, 301–318 (1975).

  66. 66

    Isaev, D. et al. Role of extracellular sialic acid in regulation of neuronal and network excitability in the rat hippocampus. J. Neurosci. 27, 11587–11594 (2007).

  67. 67

    Ednie, A. R. & Bennett, E. S. Modulation of voltage-gated ion channels by sialylation. Compr. Physiol. 2, 1269–1301 (2012).

  68. 68

    Michaluk, P. et al. Matrix metalloproteinase-9 controls NMDA receptor surface diffusion through integrin β1 signaling. J. Neurosci. 29, 6007–6012 (2009).

  69. 69

    Kochlamazashvili, G. et al. The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca2+ channels. Neuron 67, 116–128 (2010).

  70. 70

    Dityatev, A., Schachner, M. & Sonderegger, P. The dual role of the extracellular matrix in synaptic plasticity and homeostasis. Nat. Rev. Neurosci. 11, 735–746 (2010).

  71. 71

    Young, S. H. & Poo, M. M. Topographical rearrangement of acetylcholine receptors alters channel kinetics. Nature 304, 161–163 (1983).

  72. 72

    Qian, N. & Sejnowski, T. J. An electro-diffusion model for computing membrane-potentials and ionic concentrations in branching dendrites, spines and axons. Biol. Cybern. 62, 1–15 (1989). This paper provides a clear and detailed outline of the mathematical formalism of electrodiffusion pertinent to small spaces in the microenvironment of dendrites and synapses.

  73. 73

    Langlands, T. A., Henry, B. I. & Wearne, S. L. Fractional cable equation models for anomalous electrodiffusion in nerve cells: infinite domain solutions. J. Math. Biol. 59, 761–808 (2009).

  74. 74

    Henry, B. I., Langlands, T. A. & Wearne, S. L. Fractional cable models for spiny neuronal dendrites. Phys. Rev. Lett. 100, 128103 (2008).

  75. 75

    Halnes, G., Ostby, I., Pettersen, K. H., Omholt, S. W. & Einevoll, G. T. Electrodiffusive model for astrocytic and neuronal ion concentration dynamics. PLoS Comput. Biol. 9, e1003386 (2013).

  76. 76

    Halnes, G., Ostby, I., Pettersen, K. H., Omholt, S. W. & Einevoll, G. T. in Advances in Cognitive Neurodynamics (IV) (ed. Liljenström, H.) 353–360 (2015).

  77. 77

    Gianazza, E. & Righetti, P. G. Size and charge-distribution of macromolecules in living systems. J. Chromatogr. 193, 1–8 (1980).

  78. 78

    Lodish, H. F. Molecular cell biology 4th edn (W. H. Freeman, 2000).

  79. 79

    Glykys, J. et al. Local impermeant anions establish the neuronal chloride concentration. Science 343, 670–675 (2014).

  80. 80

    Voipio, J. et al. Comment on “Local impermeant anions establish the neuronal chloride concentration”. Science 345, 1130 (2014).

  81. 81

    Kaila, K., Price, T. J., Payne, J. A., Puskarjov, M. & Voipio, J. Cation-chloride cotransporters in neuronal development, plasticity and disease. Nat. Rev. Neurosci. 15, 637–654 (2014).

  82. 82

    Doyon, N., Vinay, L., Prescott, S. A. & De Koninck, Y. Chloride regulation: a dynamic equilibrium crucial for synaptic inhibition. Neuron 89, 1157–1172 (2016).

  83. 83

    Luby-Phelps, K. The physical chemistry of cytoplasm and its influence on cell function: an update. Mol. Biol. Cell 24, 2593–2596 (2013).

  84. 84

    Luby-Phelps, K. Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area. Int. Rev. Cytol. 192, 189–221 (2000).

  85. 85

    Leterrier, J. F. Water and the cytoskeleton. Cell. Mol. Biol. (Noisy-le-Grand) 47, 901–923 (2001).

  86. 86

    Fels, J., Orlov, S. N. & Grygorczyk, R. The hydrogel nature of mammalian cytoplasm contributes to osmosensing and extracellular pH sensing. Biophys. J. 96, 4276–4285 (2009).

  87. 87

    Janmey, P. A., Slochower, D. R., Wang, Y. H., Wen, Q. & Cebers, A. Polyelectrolyte properties of filamentous biopolymers and their consequences in biological fluids. Soft Matter 10, 1439–1449 (2014).

  88. 88

    Verkman, A. S. Solute and macromolecule diffusion in cellular aqueous compartments. Trends Biochem. Sci. 27, 27–33 (2002).

  89. 89

    Tuszynski, J. A., Portet, S., Dixon, J. M., Luxford, C. & Cantiello, H. F. Ionic wave propagation along actin filaments. Biophys. J. 86, 1890–1903 (2004).

  90. 90

    Kekenes-Huskey, P. M., Scott, C. E. & Atalay, S. Quantifying the influence of the crowded cytoplasm on small molecule diffusion. J. Phys. Chem. B 120, 8696–8770 (2016).

  91. 91

    Eccles, J. C. The Physiology of Synapses (Springer-Verlag, 1964).

  92. 92

    Poo, M. M. & Young, S. H. Diffusional and electrokinetic redistribution at the synapse - a physicochemical basis of synaptic competition. J. Neurobiol. 21, 157–168 (1990).

  93. 93

    Sylantyev, S. et al. Electric fields due to synaptic currents sharpen excitatory transmission. Science 319, 1845–1849 (2008). This study provided the first experimental demonstration of electrodiffusion phenomena affecting glutamatergic transmission in the synaptic cleft.

  94. 94

    Xie, Z. P. & Poo, M. M. Initial events in the formation of neuromuscular synapse - rapid induction of acetylcholine-release from embryonic neuron. Proc. Natl Acad. Sci. USA 83, 7069–7073 (1986).

  95. 95

    Groc, L. et al. Differential activity-dependent regulation of the lateral mobilities of AMPA and NMDA receptors. Nat. Neurosci. 7, 695–696 (2004).

  96. 96

    Ashby, M. C., Maier, S. R., Nishimune, A. & Henley, J. M. Lateral diffusion drives constitutive exchange of AMPA receptors at dendritic spines and is regulated by spine morphology. J. Neurosci. 26, 7046–7055 (2006).

  97. 97

    Anantharam, V. et al. Combinatorial RNA splicing alters the surface-charge on the nmda receptor. Febs Lett. 305, 27–30 (1992).

  98. 98

    Choquet, D. & Triller, A. The role of receptor diffusion in the organization of the postsynaptic membrane. Nat. Rev. Neurosci. 4, 251–265 (2003).

  99. 99

    Seeliger, C. & Le Novere, N. Enabling surface dependent diffusion in spatial simulations using Smoldyn. BMC Res. Notes 8, 752 (2015).

  100. 100

    Constals, A. et al. Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from Stargazin. Neuron 85, 787–803 (2015).

  101. 101

    Czondor, K. et al. Unified quantitative model of AMPA receptor trafficking at synapses. Proc. Natl Acad. Sci. USA 109, 3522–3527 (2012).

  102. 102

    Bliss, T. & Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331–356 (1973).

  103. 103

    Ehlers, M. D., Heine, M., Groc, L., Lee, M. C. & Choquet, D. Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activity. Neuron 54, 447–460 (2007).

  104. 104

    Meier, J., Vannier, C., Serge, A., Triller, A. & Choquet, D. Fast and reversible trapping of surface glycine receptors by gephyrin. Nat. Neurosci. 4, 253–260 (2001).

  105. 105

    Cartailler, J., Schuss, Z. & Holcman, D. Analysis of the Poisson-Nernst-Planck equation in a ball for modeling the Voltage-Current relation in neurobiological microdomains. Phys. D-Nonlinear Phenomena 339, 39–48 (2017).

  106. 106

    Cartailler, J., Schuss, Z. & Holcman, D. Electrostatics of non-neutral biological microdomains. arXiv 1612.07941 (2016). This paper provides the most complete mathematical description to date of electrolyte electrodynamics in small cellular compartments.

  107. 107

    Shilov, V., Barany, S., Grosse, C. & Shramko, O. Field-induced disturbance of the double layer electro-neutrality and non-linear electrophoresis. Adv. Colloid Interface Sci. 104, 159–173 (2003).

  108. 108

    Grienberger, C. & Konnerth, A. Imaging calcium in neurons. Neuron 73, 862–885 (2012).

  109. 109

    Bauer, M., Godec, A. & Metzler, R. Diffusion of finite-size particles in two-dimensional channels with random wall configurations. Phys. Chem. Chem. Phys. 16, 6118–6128 (2014).

  110. 110

    Zitserman, V. Y., Berezhkovskii, A. M., Pustovoit, M. A. & Bezrukov, S. M. Relaxation and fluctuations of the number of particles in a membrane channel at arbitrary particle-channel interaction. J. Chem. Phys. 129, 095101 (2008).

  111. 111

    Mak, D. O. & Webb, W. W. Conductivity noise in transmembrane ion channels due to ion concentration fluctuations via diffusion. Biophys. J. 72, 1153–1164 (1997).

  112. 112

    Das, S. Electric-double-layer potential distribution in multiple-layer immiscible electrolytes: effect of finite ion sizes. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 85, 012502 (2012). This paper presents a theoretical investigation that reveals how the size of ions can affect the electric field profile near charged cell membranes.

  113. 113

    Bialek, W. & Setayeshgar, S. Physical limits to biochemical signaling. Proc. Natl Acad. Sci. USA 102, 10040–10045 (2005).

  114. 114

    Poo, M. & Robinson, K. R. Electrophoresis of concanavalin A receptors along embryonic muscle cell membrane. Nature 265, 602–605 (1977).

  115. 115

    Mclaughlin, S. & Poo, M. M. The role of electroosmosis in the electric-field-induced movement of charged macromolecules on the surfaces of cells. Biophys. J. 34, 85–93 (1981). This work is the first study to show experimentally and to explain theoretically the effect of electro-osmosis on the lateral redistribution of membrane components.

  116. 116

    Rusakov, D. A., Savtchenko, L. P., Zheng, K. & Henley, J. M. Shaping the synaptic signal: molecular mobility inside and outside the cleft. Trends Neurosci. 34, 359–369 (2011).

  117. 117

    Linliu, S., Adey, W. R. & Poo, M. M. Migration of cell-surface concanavalin a receptors in pulsed electric-fields. Biophys. J. 45, 1211–1217 (1984).

  118. 118

    Patel, N. B. & Poo, M. M. Perturbation of the direction of neurite growth by pulsed and focal electric-fields. J. Neurosci. 4, 2939–2947 (1984).

  119. 119

    Henley, J. & Poo, M. Guiding neuronal growth cones using Ca2+ signals. Trends Cell Biol. 14, 320–330 (2004).

  120. 120

    Dufreche, J. F., Jardat, M., Turq, P. & Bagchi, B. Electrostatic relaxation and hydrodynamic interactions for self-diffusion of ions in electrolyte solutions. J. Phys. Chem. B 112, 10264–10271 (2008).

  121. 121

    Kobelev, V., Kolomeisky, A. B. & Panagiotopoulos, A. Z. Thermodynamics of electrolytes on anisotropic lattices. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 68, 066110 (2003).

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This work was supported by the Wellcome Trust Principal Fellowship, a European Research Council Advanced Grant (323113-NETSIGNAL), a Russian Science Foundation grant (15-14-30000, Fig. 1 data) and FP7 ITN (606950 EXTRABRAIN). (101896).

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The authors all researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Dmitri A. Rusakov.

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Diffusion of charged particles in electric fields.

Electrodynamic events

Time-dependent changes in electric fields or ion distributions.

Debye length

(LD). A scale over which the free charges, and therefore the electric field, are screened by an electrolytic solution.

Debye time

(tD). The average time required for an ion to travel one Debye length.

Extracellular matrix

A loose mesh, or possibly a hydrogel-like structure, composed of fibrous proteins and polysaccharides that fill the interstitial space in the brain (and other tissues).

Anisotropic media

Media that display different properties in different directions, whereas the properties of isotropic media or fields do not depend on direction.

Second-rank conductivity tensor

A measure of conductivity is a 3 × 3 array (matrix) of values that characterize medium electrical conductivity in the x, y and z directions.

Dielectric media

Media that cannot conduct electric current.

Inner Helmholtz layer

A layer that is formed in the sub-membrane space by cations that are attracted to the negatively charged cell membrane surface.

Electrical double layer

(EDL). A layer that is formed by free-diffusing electrolyte ions in the nanoscopic proximity of a charged surface, with the immediately adjacent layer of opposite-sign ions followed by a more diffuse layer of same-sign ions.

Gouy–Chapman theory

Classical formulas to describe the formation of diffuse charged layers occurring in the vicinity of a charged surface (membrane) as a result of free diffusion of small ions.

Monte Carlo

Models that rely on computational algorithms that employ random number generation to mimic naturally occurring stochastic events, such as molecular Brownian motion.

Boltzmann distribution

Sometimes called a Gibbs distribution, this is a probability distribution of the stochastically behaving particles being in a certain state.

Poisson–Boltzmann theory

Equations that describe the electrochemical potential of ions in the diffuse layer.

Continuum limit

A theoretical approximation in which, at certain limiting scale, discrete (binned) system elements are considered as a continuous parameter or feature of the system.

Van der Waals interactions

Attractive or repulsive intermolecular forces that are not related to (and are normally weaker than) covalent bonds or electrostatic forces. These interactions may include dipole interaction, hydration or lipophilicity, among others.

V*m potential

The local electric field in the membrane proximity that drives voltage sensors of ion channels and other voltage-sensitive membrane proteins.

Liquid junction potential

(LJP). A potential that arises at a non-selective boundary between two electrolytes with different ion concentrations or mobility.


A biochemical reaction in which sialic acid (an N- or O-substituted derivative of neuraminic acid) groups are introduced into oligosaccharides and carbohydrates as the terminal monosaccharide.


An intracellular or extracellular network of polymer-like molecules that often carry a high-density surface charge, with a flexible structure sensitive to the bulk pH and osmolarity.

Intracellular organelles

Specialized subunits or multi-molecular complexes that are equipped with a specific function inside a cell.

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Savtchenko, L., Poo, M. & Rusakov, D. Electrodiffusion phenomena in neuroscience: a neglected companion. Nat Rev Neurosci 18, 598–612 (2017). https://doi.org/10.1038/nrn.2017.101

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