AMYLOID-BETA PROTEIN INCREASES CA2+ CURRENTS IN RAT CEREBELLAR GRANULE NEURONS

THE effects of amyloid beta protein on voltage-sensitive Ca2+ channels were measured in cultured rat cerebellar granule neurones using the w hole-cell patch-clamp technique. Incubation of cells for 24 h with 1 m u M amyloid beta protein resulted in a 40-60% increase in the Ca2+ cha nnel current at potentials positive to 0 mV. The increase in current w as accompanied by a 5 mV shift in channel activation in the positive d irection and an increase in the rate of channel deactivation. Inhibiti on of L-type channels with 2 mu M nifedipine did not prevent the rise in Ca2+ channel current or effects on current activation and deactivat ion. The N-type Ca2+ channel antagonist omega-conotoxin GVIA (1 mu M) abolished the current increase and increase in the rate of channel dea ctivation but did not prevent the shift in the current activation curv e. These data suggest that amyloid beta protein may exert its effects on cell survival by increasing Ca2+ influx through N-type Ca2+ channel s in central neurones.