| The Voltage-Gating Process of the Voltage-Dependent Anion Channel Is Sensitive to Ion Flow Biophysical Journal, Volume 75, Issue 2, 1 August 1998, Pages 704-713 Martin Zizi, Cynthia Byrd, Roland Boxus and Marco Colombini Abstract The voltage-dependent anion channel (VDAC) is a voltage-gated channel from the mitochondrial outer membrane. It has two gating processes: one at positive potentials and the other at negative potentials. The energetics of VDAC gating are quite different when measured in the presence or absence of an ion gradient. A positive potential on the high-salt side results in channel closure at lower transmembrane potentials. The midpoint potential () shifted from 25 to 5.7mV, with an activity gradient for KCl of 0.6 versus 0.06. The opposite occurred for negative potentials on the high-salt side ( shifted from −25 to −29mV). Thus the salt gradient favored closure for one gating process and opening for the other. These results could be explained if part of the electrochemical potential of the gradients present were transferred to the gating mechanism. If the kinetic energy of the ion flow were coupled to the gating process, the effects of the gradient would depend on the mass and velocities of these ions. This was tested by using a series of different salts (KCl, NaCl, LiCl, KBr, K acetate, Na butyrate, and RbBr) under an identical activity gradient. The kinetic energy correlated very well with the measured shifts in free energy of the channel gating. This was true for both polarities. Thus the gating of VDAC is influenced by ion flow. These results are consistent in sign and direction with the voltage gating process in VDAC, which is believed to involve the movement of a positively charged portion of the wall of the channel out of the membrane. Abstract | Full Text | PDF (215 kb) |
| Electrochemical Measurement of Lateral Diffusion Coefficients of Ubiquinones and Plastoquinones of Various Isoprenoid Chain Lengths Incorporated in Model Bilayers Biophysical Journal, Volume 74, Issue 4, 1 April 1998, Pages 1937-1948 Damien Marchal, Wilfrid Boireau, Jean Marc Laval, Jacques Moiroux and Christian Bourdillon Abstract The long-range diffusion coefficients of isoprenoid quinones in a model of lipid bilayer were determined by a method avoiding fluorescent probe labeling of the molecules. The quinone electron carriers were incorporated in supported dimyristoylphosphatidylcholine layers at physiological molar fractions (<3 mol%). The elaborate bilayer template contained a built-in gold electrode at which the redox molecules solubilized in the bilayer were reduced or oxidized. The lateral diffusion coefficient of a natural quinone like UQ or PQ was 2.0±0.4×10cms at 30°C, two to three times smaller than the diffusion coefficient of a lipid analog in the same artificial bilayer. The lateral mobilities of the oxidized or reduced forms could be determined separately and were found to be identical in the 4–13pH range. For a series of isoprenoid quinones, UQ or PQ to UQ, the diffusion coefficient exhibited a marked dependence on the length of the isoprenoid chain. The data fit very well the quantitative behavior predicted by a continuum fluid model in which the isoprenoid chains are taken as rigid particles moving in the less viscous part of the bilayer and rubbing against the more viscous layers of lipid heads. The present study supports the concept of a homogeneous pool of quinone located in the less viscous region of the bilayer. Abstract | Full Text | PDF (260 kb) |
| Common Mechanism of Pore Opening Shared by Five Different Potassium Channels Biophysical Journal, Volume 90, Issue 11, 1 June 2006, Pages 3929-3940 Indira H. Shrivastava and Ivet Bahar Abstract A fundamental question associated with the function of ion channels is the conformational changes that allow for reversibly opening/occluding the pore through which the cations permeate. The recently elucidated crystal structures of potassium channels reveal similar structural motifs at their pore-forming regions, suggesting that they share a common gating mechanism. The validity of this hypothesis is explored by analyzing the collective dynamics of five known K channel structures. Normal-mode analysis using the Gaussian network model strikingly reveals that all five structures display the same intrinsic motions at their pore-forming region despite the differences in their sequences, structures, and activation mechanisms. Superposition of the most cooperative mode profiles shows that the identified common mechanism is a global corkscrew-like counterrotation of the extracellular and cytoplasmic (CP) regions, leading to the opening of the CP end of the pore. A second cooperative mode shared by all five K channels is the extension of the extracellular and/or CP ends via alternating anticorrelated fluctuations of pairs of diagonally opposite monomers. Residues acting as hinges/anchors in both modes are highly conserved across the members of the family of K channel proteins, consistent with their presently disclosed critical mechanical role in pore gating. Abstract | Full Text | PDF (1207 kb) |
Copyright © 1995 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 69, Issue 6, 2489-2500, 1 December 1995
doi:10.1016/S0006-3495(95)80119-0
Research Article
Y.A. Chizmadzhev, F.S. Cohen, A. Shcherbakov and J. Zimmerberg
Frumkin Institute of Electrochemistry, Moscow, Russia.
Once formed, fusion pores rapidly enlarge to semi-stable conductance values. The membranes lining the fusion pore are continuous bilayer structures, so variations of conductance in time reflect bending and stretching of membranes. We therefore modeled the evolution of fusion pores using the theory of the mechanics of deforming homogeneous membranes. We calculated the changes in length and width of theoretical fusion pores according to standard dynamical equations of motion. Theoretical fusion pores quickly achieve semi-stable dimensions, which correspond to energy minima located in a canyon between energy barriers. The height of the barrier preventing pore expansion diminishes along the dimensions of length and width. The bottom of the canyon slopes gently downward along increasing length. As a consequence, theoretical fusion pores slowly lengthen and widen as the dimensions migrate along the bottom of the canyon, until the barrier vanishes and the pore rapidly enlarges. The dynamics of growth is sensitive to tension, spontaneous curvature, bending elasticity, and mobilities. This sensitivity can account for the quantitative differences in pore evolution observed in two experimental systems: HA-expressing cells fusing to planar bilayer membranes and beige mouse mast cell degranulation. We conclude that the mechanics of membranes could cause the phenomenon of stagewise growth of fusion pores.