Angiotensin II-induced formation of ionic channels in bilayer lipid membranes.
The interaction of angiotensin II (ANG II) with membrane was studied by measuring conductance and current-voltage characteristics (IVC) of bilayer lipid membranes (BLM) prepared of a mixture of egg lecithin with cholesterol, and of gramicidin D-modified membranes of the same composition. Addition of physiological concentrations of ANG II (approx. 15 mumol/l) into the electrolyte (1 mol/l KCl, pH = 7) in contact with one side of BLM resulted in the appearance of discrete membrane conductance (symbol; see text) = (39.5 +/- 1.07) pS with a duration of the conductivity state tau = (52.15 +/- 6.44) s. Raising ANG II concentration to 75 mumol/l resulted in an additional conductance level of approx. 130 pS with a lifetime of approx. 1s. The electrolyte pH markedly influenced ANG II modified BLM conductance. A decrease of the electrolyte pH to 2.8 resulted in a reduction of the discrete conductance level to approx. 14 pS, whereas ANG did not induce any conductivity at pH = 11.5. The results obtained suggest that ion channels are formed consisting at least of two ANG II molecules. IVC of ANG II-modified BLM are superlinear within the range of electrolyte concentrations studied (between 0.01 and 3 mol/l KCl), i.e, the limiting stage of ion transport is the internal area of the conducting pore. ANG II affects in a cooperative manner the gramicidin D (GRD)-mediated transport, most likely by forming ANG II aggregates in the area of local inhomogeneities in the BLM structure of GRD channels.
Hianik
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T
Department of Biophysics, Faculty of Mathematics and Physics, Comenius University, Bratislava, Czechoslovakia.
Laputková
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G
D000804:Angiotensin II / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000737:chemistry; D004553:Electric Conductivity / Q000187:drug effects; D006096:Gramicidin / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008564:Membrane Potentials / Q000187:drug effects; D010713:Phosphatidylcholines / Q000737:chemistry
D007473:Ion Channels; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D000804:Angiotensin II; D006096:Gramicidin; D002784:Cholesterol