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.

Abstract

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.

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Acknowledgements

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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Glossary

Electrodiffusion

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.

Sialylation

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.

Hydrogel

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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