The Journal of Neuroscience, February 1, 1999, 19(3):906-915
Differential Modulation of Synaptic Transmission by Calcium
Chelators in Young and Aged Hippocampal CA1 Neurons: Evidence for
Altered Calcium Homeostasis in Aging
Aviv
Ouanounou1, 2, 3, 4,
Liang
Zhang1, 3,
Milton P.
Charlton1, 2, 4, and
Peter L.
Carlen1, 2, 3, 4
1 Playfair Neuroscience Unit, Toronto Hospital Research
Institute, 2 Medical Research Council Group on Nerve
Cells and Synapses, and Departments of 3 Medicine
(Neurology) and 4 Physiology, University of Toronto,
Toronto, Ontario M5T 2S8, Canada
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 µM
reduced or enhanced fEPSPs in young and aged slices, respectively, but
5',5'-dinitro BAPTA-AM (Kd of ~7000
µM) 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.
Key words:
calcium chelator; BAPTA-AM; EGTA-AM; probenecid; hippocampus; field EPSP; frequency facilitation; synaptic transmission; aging
Copyright © 1999 Society for Neuroscience 0270-6474/99/193906-10$05.00/0