Lipid Ion Channels

TL;DR

This paper reviews evidence that lipid membranes can form ion channels independently of proteins, affecting electrophysiological interpretations and highlighting the influence of thermodynamic variables and drugs on lipid channel formation.

Contribution

It introduces a thermodynamic theory of lipid channels, explaining their properties and how they are influenced by physical and chemical variables without relying on protein structures.

Findings

Lipid membranes in melting regime exhibit quantized conduction similar to protein channels.

Thermodynamic variables like temperature and pressure modulate lipid channel formation.

Drugs such as anesthetics influence lipid channel likelihood and lifetimes.

Abstract

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.