AGING CHANGES IN VOLTAGE-GATED CALCIUM CURRENTS IN HIPPOCAMPAL CA1 NEURONS

Previous current-clamp studies in rat hippocampal slice CA1 neurons ha ve found aging-related increases in long-lasting calcium (Ca)-dependen t and Ca-mediated potentials. These changes could reflect an increase in Ca influx through voltage-gated Ca channels but also could reflect a change in potassium currents. Moreover, if altered Ca influx is invo lved, it is unclear whether it arises from generally increased Ca chan nel activity, lower threshold, or reduced inactivation. To analyze the basis for altered Ca potentials, whole-cell voltage-clamp studies of CAI hippocampal neurons were performed in nondissociated hippocampal s lices of adult (3- to 5-month-old) and aged (25-to 26-month-old) rats. An aging-related increase was found in high-threshold Ca and barium ( Ba) currents, particularly in the less variable, slowly inactivating ( late) current at the end of a depolarization step. Input resistance of neurons did not differ between age groups. In steady-state inactivati on and repetitive-pulse protocols, inactivation of Ca and Ba currents was not reduced and, in some cases, was slightly greater in aged neuro ns, apparently because of larger inward current. The current blocked b y nimodipine was greater in aged neurons, indicating that some of the aging increase was in L-type currents. These results indicate that who le-cell Ca currents are increased with aging in CAI neurons, apparentl y attributable to greater channel activity rather than to reduced inac tivation. The elevated Ca influx seems likely to play a role in impair ed function and enhanced susceptibility to neurotoxic influences.