  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.
