Amyloid beta protein increases Ca2+ currents in rat cerebellar granule neurones

The effects of amyloid beta protein on voltage-sensitive Ca2+ channels were measured in cultured rat cerebellar granule neurones using the whole-cell patch-clamp technique. Incubation of cells for 24 h with 1 microM amyloid beta protein resulted in a 40-60% increase in the Ca2+ channel current at potentials positive to 0 mV. The increase in current was accompanied by a 5 mV shift in channel activation in the positive direction and an increase in the rate of channel deactivation. Inhibition of L-type channels with 2 microM nifedipine did not prevent the rise in Ca2+ channel current or effects on current activation and deactivation. The N-type Ca2+ channel antagonist omega-conotoxin GVIA (1 microM) abolished the current increase and increase in the rate of channel deactivation but did not prevent the shift in the current activation curve. These data suggest that amyloid beta protein may exert its effects on cell survival by increasing Ca2+ influx through N-type Ca2+ channels in central neurones.