| Effect of Nonuniform Interstitial Space Properties on Impulse Propagation: A Discrete Multidomain Model Biophysical Journal, Volume 95, Issue 8, 15 October 2008, Pages 3724-3737 Sarah F. Roberts, Jeroen G. Stinstra and Craig S. Henriquez Abstract This work presents a discrete multidomain model that describes ionic diffusion pathways between connected cells and within the interstitium. Unlike classical models of impulse propagation, the intracellular and extracellular spaces are represented as spatially distinct volumes with dynamic/static boundary conditions that electrically couple neighboring spaces. The model is used to investigate the impact of nonuniform geometrical and electrical properties of the interstitial space surrounding a fiber on conduction velocity and action potential waveshape. Comparison of the multidomain and bidomain models shows that although the conduction velocity is relatively insensitive to cases that confine 50% of the membrane surface by narrow extracellular depths (≥2nm), the action potential morphology varies greatly around the fiber perimeter, resulting in changes in the magnitude of extracellular potential in the tight spaces. Results also show that when the conductivity of the tight spaces is sufficiently reduced, the membrane adjacent to the tight space is eliminated from participating in propagation, and the conduction velocity increases. Owing to its ability to describe the spatial discontinuity of cardiac microstructure, the discrete multidomain can be used to determine appropriate tissue properties for use in classical macroscopic models such as the bidomain during normal and pathophysiological conditions. Abstract | Full Text | PDF (1005 kb) |
| Mechanisms of Cation Permeation in Cardiac Sodium Channel: Description by Dynamic Pore Model Biophysical Journal, Volume 77, Issue 4, 1 October 1999, Pages 1885-1904 Yasutaka Kurata, Ryoichi Sato, Ichiro Hisatome and Sunao Imanishi Abstract The selective permeability to monovalent metal cations, as well as the relationship between cation permeation and gating kinetics, was investigated for native tetrodotoxin-insensitive Na-channels in guinea pig ventricular myocytes using the whole-cell patch clamp technique. By the measurement of inward unidirectional currents and biionic reversal potentials, we demonstrate that the cardiac Na-channel is substantially permeable to all of the group Ia and IIIa cations tested, with the selectivity sequence Na≥Li>Tl>K>Rb>Cs. Current kinetics was little affected by the permeant cation species and concentrations tested (≤160mM), suggesting that the permeation process is independent of the gating process in the Na-channel. The permeability ratios determined from biionic reversal potentials were concentration and orientation dependent: the selectivity to Na increased with increasing internal [K] or external [Tl]. The dynamic pore model describing the conformational transition of the Na-channel pore between different selectivity states could account for all the experimental data, whereas conventional static pore models failed to fit the concentration-dependent permeability ratio data. We conclude that the dynamic pore mechanism, independent of the gating machinery, may play an important physiological role in regulating the selective permeability of native Na-channels. Abstract | Full Text | PDF (360 kb) |
| Wide Nanoscopic Pore of Maxi-Anion Channel Suits its Function as an ATP-Conductive Pathway Biophysical Journal, Volume 87, Issue 3, 1 September 2004, Pages 1672-1685 Ravshan Z. Sabirov and Yasunobu Okada Abstract The newly proposed function of the maxi-anion channel as a conductive pathway for ATP release requires that its pore is sufficiently large to permit passage of a bulky ATP anion. We found a linear relationship between relative permeability of organic anions of different size and their relative ionic mobility (measured as the ratio of ionic conductance) with a slope close to 1, suggesting that organic anions tested with radii up to 0.49nm (lactobionate) move inside the channel by free diffusion. In the second approach, we, for the first time, succeeded in pore sizing by the nonelectrolyte exclusion method in single-channel patch-clamp experiments. The cutoff radii of PEG molecules that could access the channel from intracellular (1.16nm) and extracellular (1.42nm) sides indicated an asymmetry of the two entrances to the channel pore. Measurements by symmetrical two-sided application of PEG molecules yielded an average functional pore radius of ∼1.3nm. These three estimates are considerably larger than the radius of ATP (0.57–0.65nm) and MgATP (∼0.60nm). We therefore conclude that the nanoscopic maxi-anion channel pore provides sufficient room to accommodate ATP and is well suited to its function as a conductive pathway for ATP release in cell-to-cell communication. Abstract | Full Text | PDF (217 kb) |
Copyright © 1964 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 4, Issue 6, 451-463, 1 November 1964
doi:10.1016/S0006-3495(64)86795-3
Articles
William J. Adelman and Robert E. Taylor
It was observed that a reduction of the sodium chloride concentration in the external solution bathing a squid giant axon by replacement with sucrose resulted in marked decreases in the peak inward and steady-state outward currents through the axon membrane following a step decrease in membrane potential. These effects are quantitatively acounted for by the increase in series resistance resulting from the decreased conductivity of the sea water and the assumption that the sodium current obeys a relation of the form I = k1C1 - k2C2 where C1, C2 are internal and external ion activities and k1, k2 are independent of concentration. It is concluded that the potassium ion current is independent of the sodium concentration. That the inward current is carried by sodium ions has been confirmed. The electrical potential (or barrier height) profile in the membrane which drives sodium ions appears to be independent of sodium ion concentration or current. A specific effect of the sucrose on hyperpolarizing currents was observed and noted but not investigated in detail.