Alamethicin channel conductance modified by lipid charge

The membrane surface charge modifies the conductance of ion channels by cha nging the electric potential and redistributing the ionic composition in th eir vicinity. We have studied the effects of lipid charge on the conductanc e of a multi-state channel formed in planar lipid bilayers by the peptide a ntibiotic alamethicin. The channel conductance was measured in two lipids: in a neutral dioleoylphosphatidylethanolamine (DOPE) and a negatively charg ed dioleoylphosphatidylserine (DOPS). The charge state of DOPS was manipula ted by the pH of the membrane-bathing solution. We find that at high salt c oncentrations (e.g., 2 M NaCl) the effect of the lipid charge is below the accuracy of our measurements. However, when the salt concentration in the m embrane-ba thing solution is decreased , the surface charge manifests itsel f as an increase in the conductance of the first two channel levels that co rrespond to the smallest conductive alamethicin aggregates. Our analysis sh ows that both the salt and pH dependence of the surface charge effect can b e rationalized within the nonlinear Poisson-Boltzmann approach. Given chann el conductance in neutral lipids, we use different procedures to account fo r the surface charge (e.g., introduce averaging over the channel aperture a nd take into account Na+ adsorption to DOPS heads), but only one adjustable parameter: an effective distance from the nearest lipid charge to the chan nel mouth center. We show that this distance varies by 0.3-0.4 nm upon chan nel transition from the minimal conducting aggregate (level LO) to the next larger one (level LI). This conclusion is in accord with a simple geometri cal model of alamethicin aggregation.