Peter C. Jordan

Relaxation studies of ion transport systems in lipid bilayer membranes.

Relaxation techniques have been widely used in kinetic studies of chemical reactions in homogeneous solution (Eigen & DeMayer, 1963). The principle of this method is well known: an external variable such as temperature or pressure is suddenly changed and the time course of a state parameter of the system such as concentration is recorded as it approaches a new steady value. Relaxation techniques can also be used for studying the rate of elementary processes in membranes. This method has proved particularly useful for the investigation of ion transport systems (ion carriers, channels, pumps) in artificial planar bilayer membranes. In this review we describe different relaxation techniques which have been developed for this purpose during the last years, as well as applications to a number of ion transport systems.

Association phenomena in a ferromagnetic colloid

We discuss the equation of state and the static correlations in a system of spherical ferromagnetic grains suspended in a magnetically passive fluid. In the domain where dipole-dipole interactions between the grains are large (low temperature) we show that the variation of the small-angle X-ray scattering with magnetic field provides a sensitive test of the model proposed to treat this system. We discuss the condensation of the grains into linear chains at low density, high magnetic field, and low temperature. The possibility of resonances in the small-angle X-ray scattering is demonstrated and certain other consequences of chain formation are indicated.

Earliest evidence for the use of pottery

Pottery was a hunter-gatherer innovation that first emerged in East Asia between 20,000 and 12,000 calibrated years before present (cal bp), towards the end of the Late Pleistocene epoch, a period of time when humans were adjusting to changing climates and new environments. Ceramic container technologies were one of a range of late glacial adaptations that were pivotal to structuring subsequent cultural trajectories in different regions of the world, but the reasons for their emergence and widespread uptake are poorly understood. The first ceramic containers must have provided prehistoric hunter-gatherers with attractive new strategies for processing and consuming foodstuffs, but virtually nothing is known of how early pots were used. Here we report the chemical analysis of food residues associated with Late Pleistocene pottery, focusing on one of the best-studied prehistoric ceramic sequences in the world, the Japanese Jōmon. We demonstrate that lipids can be recovered reliably from charred surface deposits adhering to pottery dating from about 15,000 to 11,800 cal bp (the Incipient Jōmon period), the oldest pottery so far investigated, and that in most cases these organic compounds are unequivocally derived from processing freshwater and marine organisms. Stable isotope data support the lipid evidence and suggest that most of the 101 charred deposits analysed, from across the major islands of Japan, were derived from high-trophic-level aquatic food. Productive aquatic ecotones were heavily exploited by late glacial foragers, perhaps providing an initial impetus for investment in ceramic container technology, and paving the way for further intensification of pottery use by hunter-gatherers in the early Holocene epoch. Now that we have shown that it is possible to analyse organic residues from some of the world’s earliest ceramic vessels, the subsequent development of this critical technology can be clarified through further widespread testing of hunter-gatherer pottery from later periods.

How pore mouth charge distributions alter the permeability of transmembrane ionic channels

This paper investigates the effects that surface dipole layers and surface charge layers along the pore mouth-water interface can have on the electrical properties of a transmembrane channel. Three specific molecular sources are considered: dipole layers formed by membrane phospholipids, dipole layers lining the mouth of a channel-forming protein, and charged groups in the mouth of a channel-forming protein. We find, consistent with previous work, that changing the lipid-water potential difference only influences channel conduction if the rate-limiting step takes place well inside the channel constriction. We find that either mouth dipoles or mouth charges can act as powerful ion attractors increasing either cation or anion concentration near the channel entrance to many times its bulk value, especially at low ionic strengths. The effects are sufficient to reconcile the apparently contradictory properties of high selectivity and high conductivity, observed for a number of K+ channel systems. We find that localizing the electrical sources closer to the constriction entrance substantially increases their effectiveness as ion attractors; this phenomenon is especially marked for dipolar distributions. An approximate treatment of electrolyte shielding is used to discriminate between the various mechanisms for increasing ionic concentration near the constriction entrance. Dipolar potentials are far less sensitive to ionic strength variation than potentials due to fixed charges. We suggest that the K+ channel from sarcoplasmic reticulum does not have a fixed negative charge near the constriction entrance; we suggest further that the Ca+2-activated K+ channel from transverse tubule does have such a charge.

Theoretical perspectives on ion-channel electrostatics: continuum and microscopic approaches.

Peter Lauger introduced me (P.C.J.) to the field of ion-channel electrostatics while I was a sabbatical visitor at Konstanz in 1978–79. Lauger pointed out that the relative conductance of hydrophobic ions through phosphatidyl choline (PC) and glyceryl monooleate (GMO) membranes differed by a factor of about 100 (Hladky & Haydon, 1973), quite consistent with the difference in the water-membrane potential differences in the two systems (Pickar & Benz, 1978). However, cation conductance through gramicidin channels spanning these membranes only differs by a factor of 2–3 (Bamberg et al. 1976). Why? It is the pursuit of an answer to this question which led me into my researches in this field.

Optical Spectra of Os4+ in Single Cubic Crystals at 4.2°K

The optical spectra of Os4+ (5d4) in single cubic crystals of K2PtCl6, Cs2ZrCl6, Cs2HfCl6, and Rb2ZrCl6 at 4.2°K has been studied. The spectrum is characterized by very narrow lines in the region from 10 000–36 000 cm−1. Vibrational structure is observed which may be assigned to the ungerade modes of the OsCl62− complex in the lattice. A crystal‐field analysis within the d4 manifold fits the observed ten electronic, 0–0 transitions with an rms deviation of 228 cm−1 for the parameters A = 0, B = 741, C = 1296, V = 22490, and λ5d = 2416 cm−1. The calculated molar magnetic susceptibility agrees with that found for concentrated crystals such as K2OsCl6 and Cs2OsCl6. The analysis of the electronic states was dependent upon a calculation of intensities for the t2g4 → t2g3eg transitions. The calculated results are given for a tetragonal distortion of the cubic field and are shown to qualitatively agree with the linewidth of the transitions. The calculated g values for all observed transitions are tabulated. Fina...

Electrostatic modeling of ion pores. Energy barriers and electric field profiles

This paper presents calculations of the image potential for an ion in an aqueous pore through lipid membrane and the electric field produced in such a pore when a transmembrane potential is applied. The method used is one introduced by Levitt (1978, Biophys. J. 22:209), who solved an equivalent problem, in which a surface charge density is placed at the dielectric boundary. It is shown that there are singularities in this surface charge density if the model system has sharp corners. Numerically accurate calculations require exact treatment of these singularities. The major result of this paper is the development of a projection method that explicitly accounts for this behavior. It is shown how this technique can be used to compute, both reliably and efficiently, the electrical potential within a model pore in response to any electrical source. As the length of a channel with fixed radius is increased, the peak in the image potential approaches that of an infinitely long channel more rapidly than previously believed. When a transmembrane potential is applied the electric field within a pore is constant over most of its length. Unless the channel is much longer than its radius, the field extends well into the aqueous domain. For sufficiently dissimilar dielectrics the calculated values for the peak in the image potential and for the field well within the pore can be summarized by simple empirical expressions that are accurate to within 5%.

Anion Pathway and Potential Energy Profiles along Curvilinear Bacterial ClC Cl− Pores: Electrostatic Effects of Charged Residues

X-ray structures permit theoretical study of Cl(-) permeation along bacterial ClC Cl(-) pores. We determined the lowest energy curvilinear pathway, identified anion-coordinating amino acids, and calculated the electrostatic potential energy profiles. We find that all four bacterial ClC Cl(-) crystal structures correspond to closed states. E148 and S107 side chains form steric barriers on both sides of the crystal binding site in the StClC wild-type and EcClC wild-type crystals; both the EcClC(E148A) and EcClC(E148Q) mutants are blocked at the S107 site. We studied the effect that mutating the charge of some strongly conserved pore-lining amino acids has on the electrostatic potential energy profiles. When E148 is neutralized, it creates an electrostatic trap, binding the ion near midmembrane. This suggests a possible electrostatic mechanism for controlling anion flow: neutralize E148, displace the side chain of E148 from the pore pathway to relieve the steric barrier, then trap the anion at midmembrane, and finally either deprotonate E148 and block the pore (pore closure) or bring a second Cl(-) into the pore to promote anion flow (pore conductance). Side-chain displacement may arise by competition for the binding site between the oxygens of E148 and the anion moving down the electrostatic energy gradient. We also find that the charge state of E111 and E113 may electrostatically control anion conductance and occupancy of the binding site within the cytoplasmic pore.

Polarizability effects in a four‐charge model for water

A planar four‐charge model for the water molecule, with a spherically symmetric Lennard‐Jones potential and a point polarizability, is examined. The model parameters are determined by fitting gas‐phase data for the one and two‐molecule systems. A reasonable description of water clusters of up to five molecules is obtained. The model gives qualitatively accurate properties in liquid and solid phases, but not enough condensation for agreement with experiment. It is suggested that the use of a point polarizability only partially accounts for many‐body effects. Alternatives to the above model are discussed.

How electrolyte shielding influences the electrical potential in transmembrane ion channels.

The electrical potential due to fixed charge distributions is strongly altered in the vicinity of a membrane and notably dependent on aqueous electrolyte concentration. We present an efficient way to solve the nonlinear Poisson-Boltzmann equation applicable to general cylindrically symmetric dielectric geometries. It generalizes Gouy-Chapman theory to systems containing transmembrane channels. The method is applied to three channel systems: gramicidin, gap junction, and porin. We find that for a long, narrow channel such as gramicidin concentration variation has little influence on the electrical image barrier to ion permeation. However, electrolyte shielding reduces the image induced contribution to the energy required for multiple occupancy. In addition, the presence of electrolyte significantly affects the voltage profile due to an applied potential, substantially compressing the electric field to the immediate vicinity of the pore itself. In the large diameter channels, where bulk electrolyte may be assumed to enter the pore, the electrolyte greatly reduces the image barrier to ion permeation. At physiological ionic strengths this barrier is negligible and the channel may be readily multiply occupied. At all ionic strengths considered (l greater than 0.005 M) the image barrier saturates rapidly and is essentially constant more than one channel radius from the entrance to the pore. At lower ionic strengths (l less than 0.016 M) there are noticeable (greater than 20 mV) energy penalties associated with multiple occupancy.