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D T Edmonds

Publications and source records attributed to D T Edmonds.

At least 19 recordsLinked to original sources
PubMed1998

The behaviour of ions in narrow water-filled pores.

Today, the equilibrium behavior of ions in solution may be predicted with some confidence, essentially because rapid ionic diffusion over small distances ensures homogeneity throughout the solution. Equilibrium concepts such as ionic strength and pH apply. However, when attempting to understand the behavior of ions passing rapidly through narrow pores such as ion channels, no such equilibrium state may be assumed. The passing solution may have been in equilibrium with conditions at the mouth of the pore but will not be in equilibrium with charged molecules on the pore wall. In addition, the water in narrow pores will be partially ordered by contact with the pore walls and will not behave like bulk water. To illustrate this difference, a simple equilibrium calculation of the ion concentrations near a plastic sheet penetrated by narrow pores and containing in its surface partially ionized carboxyl groups is shown to be in good agreement with experiment. However, to predict the non-equilibrium behavior within the narrow pores is much more difficult. To illustrate the difficulty, a Monte Carlo computer model is described which attempts to predict the rapid switching of ion current observed experimentally with these narrow pores.

Cell Membrane↗
PubMed1997

A novel explanation for fluctuations of ion current through narrow pores.

Fluctuation of ion current, between a high conductance and a low conductance state, through biological ion channels and pores is assumed to arise from conformational changes between an "open" and a "closed" configuration. Here we offer an additional mechanism that arises from changes in ionization of fixed charges within, or at the mouth of, a channel or pore. Our hypothesis, which is based on measurements of ion selectivity alongside ion current, applies to pores through some synthetic membranes and through channels-such as those created by certain toxins-that remain (at least partially) open in the low conductance state. It may also explain the phenomena of "open channel noise" and "substate behavior" that characterize several endogenous ion channels and should be considered when modeling the behavior of such channels.

Bacterial Toxins↗
PubMed1996

A sensitive optically detected magnetic compass for animals.

Recent experiments have indicated that at least one important magnetic compass used by many animals for navigation may be located in the eye. Here it is shown that a very sensitive magnetic compass is formed by the incorporation of a small quantity of ferrimagnetic single-domain crystals in a droplet of nematic liquid crystal. Optical detection of the compass output is illustrated by experiment and the predicted properties of a biological compass, based upon these principles, are compared with the known properties of the natural compass. Some experiments that could test the model are described.

Animals↗
PubMed1996

Linear electric traction as an alternative model of the actin/myosin motor.

Current models for the action of linear biological motors may be grouped in two main categories. The conventional "bind and bend" models rely for their power stroke upon a structural change in the myosin headgroup (S1 fragment) which follows the binding of myosin to the F-actin filament. The more recent ratchet models demonstrate that directional motion of a particle along an asymmetrical ratchet is possible with a symmetrical but time-correlated stochastic drive. In this paper a new type of model is introduced which is deterministic like the "bind and bend" model but it requires no molecular structural changes to power the stroke. Like the ratchet models the motor is driven along the linear stator by tangential forces at the interface but the forces are electrostatic and controlled by the hydrolysis of ATP to ADP.

Actins↗
PubMed1993

Rapid switching of ion current in narrow pores: implications for biological ion channels.

Ions flowing through purely synthetic filters made of polyethylene terephthalate which have been etched to produce narrow pores show: (i) rapid transitions between a high-conducting and a low-conducting state; (ii) selectivity of ion flow; and (iii) inhibition by divalent cations and protons. These features resemble those displayed by many biological ion channels. We interpret our results in terms of the special properties of ion conductance at an interface that may be observed whenever the contribution of bulk conductance is minimal.

Cations, Divalent↗
PubMed1993

Correlated ion flux through parallel pores: application to channel subconductance states.

Many ion channels that normally gate fully open or shut have recently been observed occasionally to display well-defined subconductance states with conductances much less than those of the fully open channel. One model of this behavior is a channel consisting of several parallel pores with a strong correlation between the flux in each pore such that, normally, they all conduct together but, under special circumstances, the pores may transfer to a state in which only some of them conduct. This paper introduces a general technique for modeling correlated pores, and explores in detail by computer simulation a particular model based upon electric interaction between the pores. Correlation is obtained when the transient electric field of ions passing through the pores acts upon a common set of ionizable residues of the channel protein, causing transient changes in their effective pK and hence in their charged state. The computed properties of such a correlated parallel pore channel with single occupation of each pore are derived and compared to those predicted for a single pore that can contain more than one ion at a time and also to those predicted for a model pore with fluctuating barriers. Experiments that could distinguish between the present and previous models are listed.

Animals↗
PubMed1992

Carrier-like behaviour from a static but electrically responsive model pore.

Because of the low dielectric constant of most proteins and lipids, the electric field of an ion passing through a narrow pore is long range and will interact with neighbouring ionizable residues of the channel protein. The electrical structure of the channel may thus change transiently in response to an ion passing through the pore. Model calculations then reveal that the ratio of the unidirectional ion fluxes may approach 1 as expected for a carrier or shuttling ionophore rather than the Ussing ratio expected for a pore. Saturation behaviour also becomes carrier-like. Computer simulation is reported showing a continuous variation between pore-like and carrier-like behaviour as the parameters of the system are allowed to change smoothly.

Computer Simulation↗
PubMed1990

Gating charge transfer due to fixed ionizable sites.

An alternative origin is suggested for one component of the gating charge transfer that is measured just prior to and during the opening of an ion channel. Rather than it originating solely from the motion of groups with fixed charge, some may stem from ionizable sites which remain fixed in position but change their state of charge. Such changes involve proton migration across the membrane. Two cases are discussed. In the first the ionizable group changes its charge in response to the change in its dielectric environment resulting from the formation of an aqueous pore and in the second the change is as the direct result of the applied trans-membrane voltage. Some of the predicted characteristics of this novel component of gating charge transfer are described.

Animals↗
PubMed1989

A kinetic role for ionizable sites in membrane channel proteins.

Electrically charged residues in a membrane channel protein will certainly have a direct effect upon its gating and selectivity if they are near the channel pore. It is customary to regard the charged state of such residues as a fixed feature of the channel. In this paper it is argued that far from being fixed, the charged state of ionizable residues near the pore will very probably change rapidly in response to the channel opening and to ions passing through it. Calculations are presented using simple models which demonstrate that changes in the dielectric environment and changes in the distances to other charged groups resulting from channel opening can shift the effective pK values of the sites by 3 or 4 units leading to switching of its charged state. Examples are given of how this time dependent charge state of ionizable residues may play an important role in the functioning of channels. Also, by considering the influence of the electric field due to the mobile ion upon the charge state of a residue in the channel wall, it is shown that a channel lined with acid residues may very effectively block the passage of cations while allowing the passage of anions.

Electrochemistry↗
PubMed1987

A comparison of sodium channel kinetics in the squid axon, the frog node and the frog node with BTX using the "silent gate" model.

In this paper it is shown that the very different kinetics measured for the rise of the sodium current which follows a depolarization of the membrane in the squid giant axon, the frog node and the frog node treated with Batrachotoxin may be accurately predicted using only the measured equilibrium and static characteristics for the three preparations and the kinetics measured for the gating charge transfer. The kinetic predictions follow the use of the "silent gate" model for ion channel gating. The model is electrostatic and its chief assumptions are that the channel gate, called here the N-system, has fast kinetics and responds to the gating charge that transfers but not directly to the trans-membrane voltage applied. Because channel gating, corresponding here to the motion of the N-system, does not change its energy in the trans-membrane applied electric field the gating is electrically silent as far as gating charge transfer measurement is concerned. However the probability of gating rises with the quantity of gating charge that transfers due to the electrostatic interaction between the N-system and the gating charge, redistributed under the influence of the applied trans-membrane electric field. With these assumptions the kinetics of sodium channel gating are predictable using only the static and equilibrium characteristics of gating charge and channel activation measured as a function of membrane voltage, and the kinetics of the gating charge transfer. Because of the fast kinetics assumed for the N-system the predicted kinetics are the same for channels with any number of equivalent and independent N-systems or gates acting in parallel.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

A physical model of sodium channel gating.

Most current models of membrane ion channel gating are abstract compartmental models consisting of many undefined states connected by rate constants arbitrarily assigned to fit the known kinetics. In this paper is described a model with states that are defined in terms of physically plausible real systems which is capable of describing accurately most of the static and dynamic properties measured for the sodium channel of the squid axon. The model has two components. The Q-system consists of charges and dipoles that can move in response to an electric field applied across the membrane. It would contain and may compose the gating charge that is known to transfer prior to channel opening. The N-system consists of a charged group or dipole that is constrained to move only in the plane of the membrane and thus does not interact directly with the trans-membrane electric field but can interact electrostatically with the Q-system. The N-system has only two states, its resting state (channel closed) and its excited state (channel open) and its response time is very short in comparison with that of the Q-system. On depolarizing the membrane the the N-system will not make a transition to its open state until a critical amount of Q-charge transfer has occurred. Using only four adjustable parameters that are fully determined by fitting the equilibrium properties of the model to those of the sodium channel in the squid axon, the model is then able to describe with some accuracy the kinetics of channel opening and closing and includes the Cole and Moore delay.(ABSTRACT TRUNCATED AT 250 WORDS)

Ion Channels↗
PubMed1986

A two-channel electrostatic model of an ionic counterport.

An alternative model is presented for an ionic counterport that depends upon electrostatic rather than steric forces. It consists of two passive ion channels, one selective for I-type ions and the other for J-type ions. The ions interact electrostatically such that the presence of one type of ion within its channel affects the motion of the second type of ion within its channel. In these circumstances it is possible to arrange that the spontaneous flow of I ions across the membrane, down their electrochemical potential gradient, pumps J ions in the opposite direction across the membrane, against their electrochemical gradient. To illustrate this type of model, a particular example of interionic coupling is described in which both types of ion interact with the electric dipole moments of some membrane-spanning alpha-helical sections of the counterport protein complex. By assuming that a group of four alpha-helices is free to rotate slightly about an axis perpendicular to the membrane, the desired form of coupling is obtained. Making simplifying assumptions, it is possible to calculate the kinetics of the model and to compare these with those expected in real counterports. Finally it is shown that, if the helix group rotation is powered by an external energy source, the pair of coupled passive ion channels can mimic a primary exchange pump such as Na+-K+ ATPase. Here both types of ion are propelled in opposite directions across the membrane and simultaneously against their electrochemical potential gradients.

Animals↗
PubMed1985

The alpha-helix dipole in membranes: a new gating mechanism for ion channels.

Electric dipoles placed side by side attract each other if antiparallel and repel each other if parallel. The hydrophobic alpha-helical sections of proteins that span membranes are known to possess large electric dipole moments. The first part of the paper consists of a calculation of the interaction energies between such helices including screening effects. Interaction energies remain comparable with a typical thermal energy of KT up to separations of order 20 A. In addition it is shown that, due solely to its dipole moment, an alpha-helix which completely spans the membrane has an energy up to 5 KT lower than one which terminates within the membrane width. The second part of the paper describes the electrical interaction of the charge structure of a membrane channel and the protein helices that surround the pore. The gating charge transfer that is measured when a voltage sensitive ion channel switches, means that the dipole moment of the ion channel changes. This in turn results in a change in the radial forces that act between the pore and the alpha-helices that surround it. A change in these radial forces which tend to open or to close the pore constitutes an electrically silent gating mechanism that must necessarily act subsequent to the gating charge transfer. The gating mechanism could consist of the radial translation of the neighbouring proteins or in their axial rotation under the influence of the torque that would act on a pair of approximately equidistant but oppositely directed alpha-helices. An attempt to calculate the interaction energy of a typical pore and a single alpha-helix spanning the membrane results in an energy of many times KT.

Ion Channels↗
PubMed1984

An electrostatic model of a membrane ion pump.

The model is based upon an ion channel with an electric dipolar structure. With simplifying assumptions it is possible to calculate that a typical channel, 1 nm in diameter and 5 nm long, could contain at most two or three univalent cations at a time. The channel ion binding sites have an effective affinity for ions from the fluid bathing the negative end of the channel, several orders of magnitude higher than their affinity for ions from the fluid bathing the positive end of the channel. The approach of an external, positively charged body to the negative end of the channel, is sufficient to convert the two- or three-channel ion sites with high affinity for ions from the fluid bathing this end into very low affinity sites for the same ions that now have access only to the fluid bathing the other end of the channel. The change in affinity and fluid access requires no molecular or electrical change in the channel structure other than the passive superposition of the electrostatic potential of the dipolar channel and that of the charged body. An oscillating electric field externally applied to an electric dipolar channel is shown to result in the unidirectional pumping of cations in the direction of the channel dipole even against large adverse ion concentration gradients. The energy required must be supplied by the sources of the electric field. By using two such channels in close proximity, one selective for K+ ions with its dipole moment pointing into a cell and the other selective for Na+ ions with its dipole moment pointing out from the cell, it is possible to construct a model pump with calculated properties that simulate many of those measured for Na+-K+-ATPase, with both physiological and artificial ionic concentrations.

Animals↗
PubMed1983

A Model of sodium channel-inactivation based upon the modulated blocker.

An attempt is made to model sodium channel inactivation based upon real physical processes. The principle involved, which is supported by calculation and by direct appeal to experimental results, is that the gating dipole reversal or gating charge transfer that occurs when the channel is activated, markedly modulates the electrical properties of charged groups at the channel ends. Four examples of possible mechanisms that lead to channel inactivation are described. The simple four-state model that results is able to predict: (a) the steep voltage dependence of the equilibrium inactivation characteristic without the presence of any appreciable displacement current associated with inactivation; (b) the negative shift in membrane voltage of the equilibrium inactivation characteristic relative to the activation characteristic; (c) the bell-shaped dependence of inactivation time constant on membrane voltage; (d) the similarity of the membrane voltage dependence of the time constant of recovery from inactivation, to that of inactivation itself. A brief discussion of a model for sodium channel activation based upon the same physical principle is included.

Ion Channels↗
PubMed1981

A calculation of the current voltage characteristic of a voltage-controlled model membrane ion channel.

A simple calculation is made of the current-voltage characteristic of a model ion channel in which the ion transfer rate is controlled by an electrical potential gradient rather than by mechanical gating particles. Although the model deals with sodium and potassium channels similarly, very different characteristics are obtained that approximate to those measured in the squid giant axon. The difference is due essentially to the very different Nernst potentials for these two ions. The ability of the model to predict channel activation due to both depolarization and hyperpolarizing voltage transients is described.

Animals↗