Amyloid beta-protein fragment 31-35 forms ion channels in membrane patches excised 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 amyloid beta-protein (5 microM) to either the inner or outer side of the patches, spontaneous currents could be recorded from those patches that had previously been 'silent'; (2) the fragment 31-35-induced conductance was cation-selective with a permeability ratio of P(Cs)/P(Cl)=23; (3) different levels of conductance, ranging from 25 to 500 pS, could be recorded in different patches, and in some cases, different conductances and spontaneous transitions among them could be recorded in a single patch; and (4) application of ZnCl(2) (1 mM) to the inner side of the patches reversibly blocked the newly formed channel activity; a similar effect was observed after application of CdCl(2) (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, Zn(2+)- and Cd(2+)-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 ion channels across neuronal membranes.
Qi
J S
JS
Department of Neurobiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China.
Qiao
J T
JT
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D002412:Cations; D007473:Ion Channels; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C113042:amyloid beta-protein (31-35); D002104:Cadmium; D015032:Zinc