Effects of the β-Amyloid Peptide on Membrane Ion Permeability

Several lines of evidence suggest a role for membrane ion channels in the neurotoxic effects of the β-amyloid peptide (Aβ). This chapter describes the electrophysiological techniques that can be employed to isolate and record specific membrane conductances that may be altered by Aβ. In general, an increase in conductances that cause depolarization of the cell membrane may be considered excitotoxic since they will: (1 ) increase Ca²⁺ influx through voltage-gated Ca²⁺ channels and (2) reduce Mg²⁺ -dependent block of ionotropic glutamate receptors, thereby increasing Ca²⁺ influx through N -methyl-D-aspartate (NMDA) receptor channels. Conversely, an increase in conductances that cause membrane hyperpolarization might be considered to have a protective effect. This is a simplistic view, as it has been shown that for certain forms of apoptosis an increase in hyperpolarizing K⁺ currents may be involved (1 ). It is, therefore, important to consider the functional effects of any changes in membrane conductances or ion channel currents induced by Aβ in the light of neurotoxic effects of the peptide.