Electrophysiologic properties of channels induced by Abeta25-35 in planar lipid bilayers.
Abeta25-35, a fragment of the neurotoxic amyloid beta protein Abeta1-42 found in the brain of Alzheimer patients, possesses amyloidogenic, neurotoxins and channel forming abilities similar to that of Abeta1-42. We have previously reported that Abeta25-35 formed voltage-dependent, relatively nonselective, ion-permeable channels in planar lipid bilayers. Here, we show that Abeta25-35 formed channels in both solvent-containing and solvent-free bilayers. We also report that for Abeta25-35, channel forming activity was dependent on ionic strength, membrane lipid composition, and peptide concentration, but not on pH. Lower ionic strength and negatively charged lipids increased channel formation activity, while cholesterol decreased activity. The nonlinear function relating [Abeta25-35] and membrane activity suggests that aggregation of at least three monomers is required for channel formation.
Neuroscience Interdepartmental Program, Brain Research Institute of UCLA, Los Angeles, CA, USA.
Meng-chin Allison
MC
Lin
Bruce L
BL
Kagan
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology*; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000494:pharmacology*; D010713:Phosphatidylcholines; D010743:Phospholipids / Q000737:chemistry; D012997:Solvents
D016229:Amyloid beta-Peptides; D007473:Ion Channels; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010743:Phospholipids; D012997:Solvents; C024990:asolectin