CHANNEL-FORMING ACTIVITY OF THE LOW-DENSI TY LIPOPROTEINS

The increase in the background conductivity of the bilayer lipid membr anes as well as the induction of the discrete current fluctuations, i. e. single ionic channels, as a response to the interaction of bilayers with low density lipoproteins (LDL) have been found. The mean values of the channel conductivities were 12.2 pS for LDL From healthy donors and 3.9 pS for LDL from patients with ischemic heart disease, the mem brane background conductivities being increased by 7 and 100 pS respec tively (0,1 M KCl, pH 7.4, 22 degrees C). The synthetic peptide of 11 amino acid residues that corresponds to the receptor domen (the amino acid sequence 3357-3367) of the LDL major protein (apoB-100) has provo ked single channels of 13.0 pS amplitude, whereas the background condu ctivity increased up to 200 pS. Differential scanning calorimetry of m ultilamellar liposomes from dimyristoyl phosphatidylcholine has reveal ed the decomposition of the major phase transition peak into two compo nents in the presence of the channel-forming compounds studied that al lowed the suggestion of the lateral phase separation in the lipid bila yers. The increase in the background conductivity of the membranes may be considered as a result of disordering of the lipid molecule packin g, whereas the appearance of discrete conductance fluctuations (single ion channels) may be ascribed to the formation of local defects in th e lipid bilayer structure stabilized by LDL and the receptor fragment of apoB-100.