NONLINEARITY OF CURRENT-VOLTAGE CHARACTERISTICS OF THE GRAMICIDIN CHANNEL AND THE STRUCTURE OF GRAMICIDIN MOLECULE

A sensitive method for measuring current-voltage (IV) characteristics of the type I(U) approximate to kappa U(1 + beta pU(2)) was employed to study the influence of lipid composition and cholesterol on ionic transport through gramicidin D channels. The nonlinearity coefficient beta of the IV characteristics depended on the electrolyte concentration c, the lipid composition and the cholesterol content. The value of beta was proportional to log(c) for different phospholipids. Considerable differences in beta were found for 1-palmitoyl-2-oleoyl-snglycero-3-phosphocholine (POPC) and choline plasmalogen bilayer lipid membranes (BLMs) at relatively low ionic strengths (c approximate to 0.01-0.03 M KCl). In this range beta < 0 and its absolute value was less for the POPC BLM than for choline plasmalogen. Considerable differences were also found between zwitterionic phospholipids and negatively charged soybean phosphatidylcholine (SBPC) in the concentration range tested (0.01-3 M). Also, the slope of the graph of beta versus log(c) was less for SBPC than for the other phospholipids. Almost no differences in the dependence of beta on log(c) were found between chargeless lipids (glycerolmonooleate (GMO)) and zwitterionic phospholipids. The addition of 33 mol% cholesterol to egg phosphatidylcholine (eggPC) leads to a decrease in the slope of beta versus log(c); at a higher cholesterol concentration (66 mol%) this slope changes sign and beta > 0 at all electrolyte concentrations. The value of beta correlates well with the order parameter S determined by spin probe I-12,I-3 as a function of cholesterol concentration. Presentation of experimental data in terms of the profile of standard electrochemical potential and ion-channel macromolecule shape in the framework of an electrodiffusion model of ion transport allows the influence of lipid composition and cholesterol on the gramicidin channel to be explained.