Effect of age on K+-induced cytosolic Ca2+ changes in rat cortical synaptosomes

45Ca2+ uptake and cytosolic Ca2+ concentrations [( Ca2+]i) were measured in synaptosomes prepared from the cerebral cortex of 3-, 16-, and 24-month-old male Charles River Wistar rats. Electron-microscopic examination demonstrated no morphological differences between the synaptosomes prepared from 3- and 24-month-old rats. The fast phase of Ca2+ uptake was reduced in the 24-month-old animals as compared to the 3-month-old ones (-23%, p less than 0.001), whereas no difference was found between the 16- and the 3-month-old rats. Age did not modify [Ca2+]i, as measured by the quin 2 technique, both at rest and immediately after depolarization with 50 mM K+. The Ca2+ load following depolarization was cleared in about 13 min in the 3-month-old rats. The rate of clearance was significantly slower both in the 16- (p less than 0.01) and in the 24-month-old rats (p less than 0.0001). The addition of verapamil (60 microM) after depolarization restored [Ca2+]i to resting level in aged rats at the same rate as in young rats. A prolonged Ca2+ influx, therefore, may be responsible for the slower clearance of Ca2+ load in aged rats.