Lipid Ion Channels

The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels, their properties and the physical chemistry underlying their creation. We introduce into the thermodynamic theory of membrane fluctuations from which the lipid channels originate. Furthermore, we demonstrate how the appearance of lipid channels can be influenced by the alteration of the thermodynamic variables (temperature, pressure, tension, chemical potentials) in a coherent description that is free of parameters. This description leads to pores that display dwell times closely coupled to the fluctuation lifetime via the fluctuation-dissipation theorem. Drugs as anesthetics and neurotransmitters are shown to influence the channel likelihood and their lifetimes in a predictable manner. We also discuss the role of proteins in influencing the likelihood of lipid channel formation.Comment: Revie

Linear nonequilibrium thermodynamics of reversible periodic processes and chemical oscillations

Onsager's phenomenological equations successfully describe irreversible thermodynamic processes. They assume a symmetric coupling matrix between thermodynamic fluxes and forces. It is easily shown that the antisymmetric part of a coupling matrix does not contribute to dissipation. Therefore, entropy production is exclusively governed by the symmetric matrix even in the presence of antisymmetric terms. In this work we focus on the antisymmetric contributions which describe isentropic oscillations and well-defined equations of motion. The formalism contains variables that are equivalent to momenta, and coefficients that are analogous to an inertial mass. We apply this formalism to simple problems such as an oscillating piston and the oscillation in an electrical LC-circuit. We show that isentropic oscillations are possible even close to equilibrium in the linear limit and one does not require far-from equilibrium situations. One can extend this formalism to other pairs of variables, including chemical systems with oscillations. In isentropic thermodynamic systems all extensive and intensive variables including temperature can display oscillations reminiscent of adiabatic waves.Comment: 11 pages, 5 figure

Periodic solutions and refractory periods in the soliton theory for nerves and the locust femoral nerve

Close to melting transitions it is possible to propagate solitary electromechanical pulses which reflect many of the experimental features of the nerve pulse including mechanical dislocations and reversible heat production. Here we show that one also obtains the possibility of periodic pulse generation when the boundary condition for the nerve is the conservation of the overall length of the nerve. This condition generates an undershoot beneath the baseline (`hyperpolarization') and a `refractory period', i.e., a minimum distance between pulses. In this paper, we outline the theory for periodic solutions to the wave equation and compare these results to action potentials from the femoral nerve of the locust (locusta migratoria). In particular, we describe the frequently occurring minimum-distance doublet pulses seen in these neurons and compare them to the periodic pulse solutions.Comment: 10 pages, 6 Figure

The capacitance and electromechanical coupling of lipid membranes close to transitions. The effect of electrostriction

Biomembranes are thin capacitors with the unique feature of displaying phase transitions in a physiologically relevant regime. We investigate the voltage and lateral pressure dependence of their capacitance close to their chain melting transition. Since the gel and the fluid membrane have different area and thickness, the capacitance of the two membrane phases is different. In the presence of external fields, charges exert forces that can influence the state of the membrane, thereby influencing the transition temperature. This phenomenon is called electrostriction. We show that this effect allows us to introduce a capacitive susceptibility that assumes a maximum in the melting transition with an associated excess charge. As a consequence, there exist voltage regimes where a small change in voltage can lead to a large uptake of charge and a large capacitive current. Furthermore, we consider electromechanical behavior such as pressure-induced changes in capacitance, and the application of such concepts in biology.Comment: 5 figure

Lipid ion channels and the role of proteins

Synthetic lipid membranes in the absence of proteins can display quantized conduction events for ions that are virtually indistinguishable from those of protein channel. By indistinguishable we mean that one cannot decide based on the current trace alone whether conductance events originate from a membrane, which does or does not contain channel proteins. Additional evidence is required to distinguish between the two cases, and it is not always certain that such evidence can be provided. The phenomenological similarities are striking and span a wide range of phenomena: The typical conductances are of equal order and both lifetime distributions and current histograms are similar. One finds conduction bursts, flickering, and multistep-conductance. Lipid channels can be gated by voltage, and can be blocked by drugs. They respond to changes in lateral membrane tension and temperature. Thus, they behave like voltage-gated, temperature-gated and mechano-sensitive protein channels, or like receptors. Lipid channels are remarkably under-appreciated. However, the similarity between lipid and protein channels poses an eminent problem for the interpretation of protein channel data. For instance, the Hodgkin-Huxley theory for nerve pulse conduction requires a selective mechanism for the conduction of sodium and potassium ions. To this end, the lipid membrane must act both as a capacitor and as an insulator. Non-selective ion conductance by mechanisms other than the gated protein-channels challenges the proposed mechanism for pulse propagation. ... Some important questions arise: Are lipid and protein channels similar due a common mechanism, or are these similarities fortuitous? Is it possible that both phenomena are different aspects of the same phenomenon? Are lipid and protein channels different at all? ... (abbreviated)Comment: 10 pages, 10 figures - accepted by 'Accounts of Chemical Research

The thermodynamics of general and local anesthesia

General anesthetics are known to cause depression of the freezing point of transitions in biomembranes. This is a consequence of ideal mixing of the anesthetic drugs in the membrane fluid phase and exclusion from the solid phase. Such a generic law provides physical justification of the famous Meyer-Overton rule. We show here that general anesthetics, barbiturates and local anesthetics all display the same effect on melting transitions. Their effect is reversed by hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is very similar to that of general anesthetics. We present a detailed thermodynamic analysis of heat capacity profiles of membranes in the presence of anesthetics. This analysis is able to describe experimentally observed calorimetric profiles and permits prediction of the anesthetic features of arbitrary molecules. In addition, we discuss the thermodynamic origin of the cutoff-effect of long-chain alcohols and the additivity of the effect of general and local anesthetics.Comment: 12 pages, 9 figures, 1 tabl

The stability of solitons in biomembranes and nerves

We examine the stability of a class of solitons, obtained from a generalization of the Boussinesq equation, which have been proposed to be relevant for pulse propagation in biomembranes and nerves. These solitons are found to be stable with respect to small amplitude fluctuations. They emerge naturally from non-solitonic initial excitations and are robust in the presence of dissipation.Comment: 7 pages, 5 figure

Ion-channel-like behavior in lipid bilayer membranes at the melting transition

It is well known that at the gel-liquid phase transition temperature a lipid bilayer membrane exhibits an increased ion permeability. We analyze the quantized currents in which the increased permeability presents itself. The open time histogram shows a "-3/2" power law which implies an open-closed transition rate that decreases like $k(t) \propto t^{-1}$ as time evolves. We propose a "pore freezing" model to explain the observations. We discuss how this model also leads to the $1/f^{\alpha}$ noise that is commonly observed in currents across biological and artificial membranes.Comment: 5 pages, 4 figure