Lipid ion channels

Abstract

The interpretation of 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 (e.g., temperature, pressure, tension and 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.

Imaging the dynamics of individual electropores

“…V c was found to be 224 ± 39 mV (n = 17) when the agarose and droplet contained 1.5 M KCl, and 272 ± 29 mV (n = 7) when the agarose contained 750 mM CaCl 2 . The apparent stabilizing effect of calcium is perhaps a result of the divalent cation having a stronger electrostatic interaction with the lipid head groups than K + , as has been reported in other membrane systems (22).…”

“…Increasing the applied potential difference is predicted to lower and broaden the local energy minimum that supports the hydrophilic pore, and lower the barrier to unbounded pore expansion. electrical recording (5,22,23); however, here, by isolating individual oSCR signals, we are able to extend observation of these phenomena to higher potentials, where the individual signals would be obscured in a purely electrical measurement. We have observed that all of these modes can occur at elevated potentials, with no apparent favor of one mode over another.…”

“…The transient nature and small size of electropores place significant limitations on the measurement of electropore dynamics, and more fundamentally on their direct detection. Electrical single-channel recording (SCR) can resolve these dynamics at high time resolution (22,23); however, SCR is limited in that it can only detect the total current across the membrane, and is thus unable to resolve whether conductance events are due to single or multiple permeabilization events. Indeed, the most common characteristic for electroporation in SCR would be a "noisy" trace that precedes bilayer rupture (see Fig.…”

Chloroform alters interleaflet coupling in lipid bilayers: an entropic mechanism

“…The molecular mechanism of general anaesthesia is still an unresolved issue. Some proposals suggest that the anaesthetic compound changes the phasic state of the cell membrane, altering the activity of the lipid [50] and/ or protein [51] ion channels involved in nerve transmission. Another aspect to take into account is that membrane proteins are distributed in a heterogeneous manner in the cell membrane and that alterations of this distribution may modify their functionality.…”

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

“…In particular, one finds a straight-forward explanation of these quantized current events in inevitable thermodynamic fluctuations. (For a review, see [37]). Thus, during the pulse propagation, one expects that the lipid membrane should become permeable for ions and that quantized conduction events should occur.…”