AGGREGATES OF A BETA-AMYLOID PEPTIDE ARE REQUIRED TO INDUCE CALCIUM CURRENTS IN NEURON-LIKE HUMAN TERATOCARCINOMA CELLS - RELATION TO ALZHEIMERS-DISEASE

We report that human hNT cells display neuron-like calcium channel act ivation. Patch-clamp experiments show that exposure of hNT cells to th e Alzheimer-related amyloid peptide beta AP(25-35) induces large and i rreversible inward calcium currents at -80 mV in whole cell mode, with a linear current-voltage relationship. This behavior is suggestive of ionophore formation. An analogous peptide with scrambled sequence has no effect. These ionophore effects by the beta AP(25-35) peptide, the first report in a human cell-line, are very rapid effects. The curren ts are large and stable, and are blocked by Al3+ but not by Cd2+. Filt ration removes a peptide aggregate from the amyloid peptide beta AP(25 -35) solution and thereby abolishes the inward current. The residual s oluble peptide has no effect. These data suggest that the initial step of the neurotoxic effect of beta AP(25-35) may be due to the insertio n of the aggregated peptide into the cellular membrane as a Ca2+-carry ing ionophore. The relevance of calcium-mediated cell death, especiall y in Alzheimer's disease, is discussed.