Protein Kinase C Involvement in the Acetylcholine Release Reduction Induced by Amyloid-beta(25-35) Aggregates on Neuromuscular Synapses

Using intracellular recording of the diaphragm muscle of adult rats, we have investigated the short-term functional effects of amyloid-beta (A beta)(25-35) peptide aggregates on the modulation of acetylcholine (ACh) release and the involvement of protein kinase C (PKC). The non-aggregated form of this peptide does not change the evoked and spontaneous transmitter release parameters on the neuromuscular synapse. However, the aggregated form of A beta(25-35) acutely interferes with evoked quantal ACh release (similar to 40% reduction) when synaptic activity in the ex vivo neuromuscular preparation is maintained by low frequency (1 Hz) electrical stimulation. This effect is partially dependent on the activity of PKC that may have a permissive action. The end result of A beta(25-35) is in opposition to the PKC-dependent maintenance effect on ACh release manifested in active synapses.