CHANGES OF THE MEMBRANE-POTENTIAL PROFILE INDUCED BY VERAPAMIL AND PROPRANOLOL

The effects of the organic calcium channel blocker verapamil and the b eta-receptor blocker propranolol on dipole (phi(d)) and surface (phi(s )) potentials of bilayer lipid membranes were studied. The boundary po tentials (phi(b) = phi(d)+phi(s)) of black lipid membranes, monitored by conductance measurements in the presence of nonactin and by capacit ive current measurements were compared with phi(s) calculated from the electrophoretic mobility of lipid vesicles. It was shown that the inc rease of boundary potential, induced by the adsorption of the positive ly charged propranolol, was caused solely by an increase in surface po tential. Although phi(s) also increases due to the adsorption of verap amil, phi(b) diminishes. A sharp decrease of the dipole potential was shown to be responsible for this effect. From Langmuir adsorption isot herm the dissociation constant K-d of verapamil was estimated. The unc harged form of verapamil (K-d = (0.061 +/- 0.01) mM at pH 10.5) has a tenfold higher affinity to a neutral bilayer membrane than the positiv ely charged form. The alteration of membrane dipole potential due to v erapamil adsorption may have important implications for both membrane translocation and partitioning of small or hydrophobic ions and charge d groups of membrane proteins. (C) 1998 Elsevier Science B.V. All righ ts reserved.