Influence of Fixed Charge and Polyunsaturated Compounds on the Monomolecular Gramicidin Channel Function in Phospholipid Monolayers: Further Studies

Abstract

An investigation into the effect of adsorbed and incorporated fixed charge and incorporated polyunsaturated compounds in dioleoylphosphatidylcholine (DOPC) monolayers on the translocation of Tl+ through the monomolecular gramicidin channel is reported in this paper. The work also includes a study of the interaction of the tricyclic neuroleptic drug chlorpromazine with DOPC monolayers and the influence of chlorpromazine on the transport of Tl+ through the gramicidin channel. Techniques used were out-of-phase AC voltammetry and cyclic voltammetry and chronoamperometry of the Tl(I)/Tl(Hg) couple. It was shown that negatively charged phosphatidylserine (PS) when incorporated into DOPC layers increases the gramicidin-mediated permeability of the layers by increasing the concentration of Tl+ on the monolayer surface and increasing the rate of translocation of the ion in the channel. Positively charged ions which adsorb onto lipid layers have the opposite effect. Polyunsaturated compounds when incorporated into DOPC monolayers have influences on gramicidin-mediated Tl+ translocation similar to those of negative fixed charge. The chlorpromazine interaction with DOPC layers and its influence on the transport of Tl+ in the pore depends on its charge. At high solution pH above its pKa of 9.3 its effect on the gramicidin-mediated permeability is similar to that of a polyunsaturated compound. At low solution pH its positive charge dominates its influence on the transport of Tl+ in the channel, decreasing the gramicidin-mediated permeability.