The thermodynamics of lipid ion channel formation in the absence and presence of anesthetics. BLM experiments and simulations

TL;DR

This study investigates lipid membrane permeability and pore formation during melting transitions, showing that anesthetics influence membrane thermodynamics and permeability by modifying heat capacity and area fluctuations, supported by experiments and thermodynamic modeling.

Contribution

It provides a combined experimental and thermodynamic model analysis of lipid ion channel formation and anesthetic effects on membrane permeability.

Findings

Pores are approximately one lipid cross-section in size.

Pore formation correlates with increased lateral compressibility.

Anesthetics shift heat capacity profiles, affecting permeability.

Abstract

It is known that lipid membranes become permeable in their melting regime. In microscopic conductance measurements on black lipid membranes one finds that conduction takes place via quantized events closely resembling those reported for protein ion channels. Here, we present data of ion currents through black lipid membranes in the presence and absence of the anesthetics octanol and ethanol, and compare them to a statistical thermodynamics model using parameters that are obtained from experimental calorimetric data. The conductance steps in pure lipid membrane suggest aqueous pores with the size of approximately one lipid cross-section. We model the permeability by assuming empty sites of the size of one lipid. We find that pore formation in the melting transition regime is facilitated by the increase of the lateral compressibility that expresses itself in the area fluctuations. Thus, pore formation is related to critical opalescence in two dimensions. Anesthetics alter the permeability by affecting the thermodynamic state of the membrane and by shifting the heat capacity profiles.