Amyloid beta-protein fragment 31-35 forms ion channels in membrane patchesexcised from rat hippocampal neurons

Inside-out membrane patches excised from rat hippocampal neurons were used to test if ion channels could be formed by fragment 31-35 of amyloid beta - protein. The results showed: (1) after application of fragment 31-35 of amy loid beta -protein (5 muM) to either the inner or outer side of the patches , spontaneous currents could be recorded from those patches that had previo usly been 'silent'; (2) the fragment 31-35-induced conductance was cation-s elective with a permeability ratio of P-Cs/P-Ci = 23; (3) different levels of conductance, ranging from 25 to 500 pS, could be recorded in different p atches, and in some cases, different conductances and spontaneous transitio ns among them could be recorded in a single patch; and (4) application of Z nCl2 (1 mM) to the inner side of the patches reversibly blocked the newly f ormed channel activity; a similar effect was observed after application of CdCl2 (1 MM). These results show that fragment 31-35 of amyloid beta -protein can insert into membrane patches from both sides and form cation-selective, Zn2+- and Cd2+-sensitive ion channels. It is proposed that fragment 31-35 in amyloid beta -protein might be the shortest active sequence known to date to form i on channels across neuronal membranes. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.