Amyloid beta protein-induced irreversible current in rat cortical neurones.

The effect of amyloid beta protein (A beta P) was examined in neurones dissociated from rat cortex using the nystatin perforated patch-clamp technique. A beta P at concentrations > 10 nM induced an irreversible slow inward current associated with an increase in membrane conductance. The time lag until the appearance of the effect of A beta P shortened in a concentration-dependent manner. When extracellular Na+ and Cl-, and intracellular K+ were replaced by equimolar N-methyl glucamine, isothionate- and Cs+, respectively, the membrane conductance and the reversal potential were not affected. Even when an internal solution including 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (20 mM) was used, the effect of A beta P did not alter. It is suggested that A beta P binds to the neuronal membrane and opens non-selective ion channels, resulting in neuronal degeneration.