Changes of the membrane potential profile induced by verapamil and propranolol.
The effects of the organic calcium channel blocker verapamil and the beta-receptor blocker propranolol on dipole (phi(d)) and surface (phi(s)) potentials of bilayer lipid membranes were studied. The boundary potentials (phi(b)= phi(d) + phi(s)) of black lipid membranes, monitored by conductance measurements in the presence of nonactin and by capacitive current measurements were compared with phi(s) calculated from the electrophoretic mobility of lipid vesicles. It was shown that the increase of boundary potential, induced by the adsorption of the positively charged propranolol, was caused solely by an increase in surface potential. Although phi(s) also increases due to the adsorption of verapamil, phi(b) diminishes. A sharp decrease of the dipole potential was shown to be responsible for this effect. From Langmuir adsorption isotherm the dissociation constant Kd of verapamil was estimated. The uncharged form of verapamil (Kd=(0.061+/-0.01) mM at pH 10.5) has a tenfold higher affinity to a neutral bilayer membrane than the positively charged form. The alteration of membrane dipole potential due to verapamil adsorption may have important implications for both membrane translocation and partitioning of small or hydrophobic ions and charged groups of membrane proteins.
Pohl
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Department of Medical Physics and Biophysics, Martin-Luther University, 06097 Halle/Saale, Germany. elena.pohl@medizin.uni-halle.de
Krylov
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Block
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Pohl
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D008051:Lipid Bilayers; D011433:Propranolol; D014700:Verapamil