Differential Modulation of Synaptic Transmission by Calcium Chelators in Young and Aged Hippocampal CA1 Neurons: Evidence for Altered Calcium Homeostasis in Aging

The effects of membrane-permeant Ca2+ chelators on field EPSPs (fEPSPs) were measured in the hippocampal CA1 region of brain slices from young (2-4 months) and old (24-27 months) Fischer 344 rats. BAPTA-AM depressed fEPSPs in young slices by up to 70% but enhanced fEPSPs by 30% in aged slices. EGTA-AM, with slower binding kinetics, did not affect fEPSPs from young slices but enhanced fEPSPs in aged slices. BAPTA derivatives with calcium dissociation constants (Kd) of 0.2-3.5 microM reduced or enhanced fEPSPs in young and aged slices, respectively, but 5',5'-dinitro BAPTA-AM (Kd of approximately 7000 microM) had no effect. Frequency facilitation of the fEPSPs occurred in young, but not in aged, slices, except when BAPTA-AM or EGTA-AM was perfused onto aged slices. The differential effects of BAPTA-AM in young and old slices were eliminated by perfusing with a low Ca2+-high Mg2+ saline or with the calcium blocker Co2+. These data suggest that intracellular Ca2+ regulation is altered and raised in aged neurons. Cell-permeant calcium buffers may be able to "ameliorate" deficits in synaptic transmission in the aged brain.