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 t o study the influence of lipid composition and cholesterol on ionic tr ansport through gramicidin D channels. The nonlinearity coefficient be ta of the IV characteristics depended on the electrolyte concentration c, the lipid composition and the cholesterol content. The value of be ta was proportional to log(c) for different phospholipids. Considerabl e 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 a lso found between zwitterionic phospholipids and negatively charged so ybean phosphatidylcholine (SBPC) in the concentration range tested (0. 01-3 M). Also, the slope of the graph of beta versus log(c) was less f or SBPC than for the other phospholipids. Almost no differences in the dependence of beta on log(c) were found between chargeless lipids (gl ycerolmonooleate (GMO)) and zwitterionic phospholipids. The addition o f 33 mol% cholesterol to egg phosphatidylcholine (eggPC) leads to a de crease in the slope of beta versus log(c); at a higher cholesterol con centration (66 mol%) this slope changes sign and beta > 0 at all elect rolyte concentrations. The value of beta correlates well with the orde r parameter S determined by spin probe I-12,I-3 as a function of chole sterol concentration. Presentation of experimental data in terms of th e profile of standard electrochemical potential and ion-channel macrom olecule shape in the framework of an electrodiffusion model of ion tra nsport allows the influence of lipid composition and cholesterol on th e gramicidin channel to be explained.