Aging of voltage-dependent calcium channels in brain synapses

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We have found age-related changes in synaptic functions, that is, decreased release of acetylcholine from synapses and diminished influx of calcium ion through voltage-dependent calcium channels. Furthermore, the efficacy of calcium channels were shown to be restored with sialyl compounds.The activities of acetylcholine synthesis and rlease were examined using synaptosomes. It wss found that the synthetic rate of acetylcholine was maintained the same in aged synapses as in young, and that acetylcholine release evoked by depolarization was decreased. It is known that the exositosis of transmitters is triggered by calcium ion coming in through calcium channels. In fact, calcium influx was found to decrease in aged synaptosomes as monitored using Fura-2. Thus, these observations may indicate that dimished influx of calcium ion through calcium channesl underly the decreased release of acetylcholine in aged synapses.To restore the decreased release of acetylcholine, the enhancement of calcium influx was attempted by modifying the channel efficacy. Sialyl compounds such as gangliosides and their synthetic analogues which have high affinity to calcium have been found to enhance calcium influx. These results suggest that sialyl compounds may restore the decreased synaptic functions in aging.