A Poisson–Nernst–Planck Model for Biological Ion Channels—An Asymptotic Analysis in a Three-Dimensional Narrow Funnel (original) (raw)
Related papers
European Journal of Applied Mathematics, 2008
Ion channels are proteins with a narrow hole down their middle that control a wide range of biological function by controlling the flow of spherical ions from one macroscopic region to another. Ion channels do not change their conformation on the biological time scale once they are open, so they can be described by a combination of Poisson and driftdiffusion (Nernst-Planck) equations called PNP in biophysics. We use singular perturbation techniques to analyse the steady-state PNP system for a channel with a general geometry and a piecewise constant permanent charge profile. We construct an outer solution for the case of a constant permanent charge density in three dimensions that is also a valid solution of the one-dimensional system. The asymptotical current-voltage (I-V ) characteristic curve of the device (obtained by the singular perturbation analysis) is shown to be a very good approximation of the numerical I-V curve (obtained by solving the system numerically). The physical constraint of non-negative concentrations implies a unique solution, i.e., for each given applied potential there corresponds a unique electric current (relaxing this constraint yields non-physical multiple solutions for sufficiently large voltages).
Numerical methods for a Poisson-Nernst-Planck-Fermi model of biological ion channels
Physical review. E, Statistical, nonlinear, and soft matter physics, 2015
Numerical methods are proposed for an advanced Poisson-Nernst-Planck-Fermi (PNPF) model for studying ion transport through biological ion channels. PNPF contains many more correlations than most models and simulations of channels, because it includes water and calculates dielectric properties consistently as outputs. This model accounts for the steric effect of ions and water molecules with different sizes and interstitial voids, the correlation effect of crowded ions with different valences, and the screening effect of polarized water molecules in an inhomogeneous aqueous electrolyte. The steric energy is shown to be comparable to the electrical energy under physiological conditions, demonstrating the crucial role of the excluded volume of particles and the voids in the natural function of channel proteins. Water is shown to play a critical role in both correlation and steric effects in the model. We extend the classical Scharfetter-Gummel (SG) method for semiconductor devices to i...
Permeation through an open channel: Poisson-Nernst-Planck theory of a synthetic ionic channel
Biophysical Journal, 1997
The synthetic channel [acetyl-(LeuSerSerLeuLeuSerLeu)3-CONH2]6 (pore diameter -8 A, length -30 A) is a bundle of six a-helices with blocked termini. This simple channel has complex properties, which are difficult to explain, even qualitatively, by traditional theories: its single-channel currents rectify in symmetrical solutions and its selectivity (defined by reversal potential) is a sensitive function of bathing solution. These complex properties can be fit quantitatively if the channel has fixed charge at its ends, forming a kind of macrodipole, bracketing a central charged region, and the shielding of the fixed charges is described by the Poisson-Nernst-Planck (PNP) equations. PNP fits current voltage relations measured in 15 solutions with an r.m.s. error of 3.6% using four adjustable parameters: the diffusion coefficients in the channel's pore DK = 2.1 x 10-6 and Dc, = 2.6 x 10-7 cm2/s; and the fixed charge at the ends of the channel of ±0.1 2e (with unequal densities 0.71 M = 0.021e/A on the N-side and -1.9 M = -0.058e/A on the C-side). The fixed charge in the central region is 0.31e (with density P2 = 0.47 M = 0.014e/A). In contrast to traditional theories, PNP computes the electric field in the open channel from all of the charges in the system, by a rapid and accurate numerical procedure. In essence, PNP is a theory of the shielding of fixed (i.e., permanent) charge of the channel by mobile charge and by the ionic atmosphere in and near the channel's pore. The theory fits a wide range of data because the ionic contents and potential profile in the channel change significantly with experimental conditions, as they must, if the channel simultaneously satisfies the Poisson and Nemst-Planck equations and boundary conditions. Qualitatively speaking, the theory shows that small changes in the ionic atmosphere of the channel (i.e., shielding) make big changes in the potential profile and even bigger changes in flux, because potential is a sensitive function of charge and shielding, and flux is an exponential function of potential.
A numerical solver of 3D Poisson Nernst Planck equations for functional studies of ion channels
Modelling in Medicine and Biology VI, 2005
Recent results of X-Ray crystallography have provided important information for functional studies of membrane ion channels based on computer simulations. Because of the large number of atoms that constitute the channel proteins, it is prohibitive to approach functional studies using molecular dynamic methods. To overcome the current computational limit we propose a novel approach based on the Poisson, Nernst, Planck electrodiffusion theory. The proposed numerical method allows the quick computation of ion flux through the channel, starting from its 3D structure. We applied the method to the KcsA potassium channel obtaining a good accordance with the experimental data.
Dielectric Self-Energy in Poisson-Boltzmann and Poisson-Nernst-Planck Models of Ion Channels
Biophysical Journal, 2003
We demonstrated previously that the two continuum theories widely used in modeling biological ion channels give unreliable results when the radius of the conduit is less than two Debye lengths. The reason for this failure is the neglect of surface charges on the protein wall induced by permeating ions. Here we attempt to improve the accuracy of the Poisson-Boltzmann and Poisson-Nernst-Planck theories, when applied to channel-like environments, by including a specific dielectric self-energy term to overcome spurious shielding effects inherent in these theories. By comparing results with Brownian dynamics simulations, we show that the inclusion of an additional term in the equations yields significant qualitative improvements. The modified theories perform well in very wide and very narrow channels, but are less successful at intermediate sizes. The situation is worse in multi-ion channels because of the inability of the continuum theories to handle the ion-to-ion interactions correctly. Thus, further work is required if these continuum theories are to be reliably salvaged for quantitative studies of biological ion channels in all situations.
Biophysical Journal, 2000
Continuum theories of electrolytes are widely used to describe physical processes in various biological systems. Although these are well-established theories in macroscopic situations, it is not clear from the outset that they should work in small systems whose dimensions are comparable to or smaller than the Debye length. Here, we test the validity of the mean-field approximation in PoissonϪBoltzmann theory by comparing its predictions with those of Brownian dynamics simulations. For this purpose we use spherical and cylindrical boundaries and a catenary shape similar to that of the acetylcholine receptor channel. The interior region filled with electrolyte is assumed to have a high dielectric constant, and the exterior region representing protein a low one. Comparisons of the force on a test ion obtained with the two methods show that the shielding effect due to counterions is overestimated in PoissonϪBoltzmann theory when the ion is within a Debye length of the boundary. As the ion gets closer to the boundary, the discrepancy in force grows rapidly. The implication for membrane channels, whose radii are typically smaller than the Debye length, is that PoissonϪBoltzmann theory cannot be used to obtain reliable estimates of the electrostatic potential energy and force on an ion in the channel environment.
Mathematical models of ion transport through cell membrane channels
Mathematica Applicanda, 2014
We discuss various models of ion transport through cell membrane channels. Recent experimental data shows that sizes of some ion channels are compared to those of ions and that only few ions may be simultaneously in any single channel. Theoretical description of ion transport in such channels should therefore take into account stochastic fluctuations and interactions between ions and between ions and channel proteins. This is not satisfied by macroscopic continuum models based on the Poisson-Nernst-Planck equations. More realistic descriptions of ion transport are offered by microscopic molecular and Brownian dynamics. We present a derivation of the Poisson-Nernst-Planck equations. We also review some recent models such as single-file diffusion and Markov chains of interacting ions (boundary driven lattice gases). Such models take into account discrete and stochastic nature of ion transport and specifically interactions between ions in ion channels.
2009
A self-consistent solution is derived for the Poisson-Nernst-Planck (PNP) equation, valid both inside a biological ion channel and in the adjacent bulk fluid. An iterative procedure is used to match the two solutions together at the channel mouth. Charge fluctuations at the mouth are modeled as shot noise flipping the height of the potential barrier at the selectivity site. The resultant estimates of the conductivity of the ion channel are in good agreement with Gramicidin experimental measurements and they reproduce the observed current saturation with increasing concentration.