Age-related decrease in brain synaptic membrane Ca2+-ATPase in F344/BNF1 rats

We used Fisher 344/Brown Norway hybrid rats (F344/BNF1) to determine whethe r previously reported decreases in brain synaptic plasma membrane (SPM) Ca2 +-ATPase activity in inbred F344 rats also occurred in the hybrids. Plasma membrane Ca2+-ATPase (PMCA) activity in SPMs from F344/BNF1 rat brains show ed a progressive age-dependent decrease in V-max from 60.9 +/- 3.7 nmol Pi/ mg/min (n = 6) in 5-month rats to 32.4 +/- 3.6 nmol Pi/mg/min (n = 6) in 34 -month animals, with no change in K-act for Ca2+. Immunoreactive PMCA in SP Ms also decreased by similar to 20% at 34 months, and the calmodulin (CaM) bound to membranes following extraction with EDTA also declined progressive ly with age. The effectiveness of CaM in stimulating PMCA activity was sign ificantly lower when CaM was purified from the brains of old vs. young F344 rats and when CaM from 5-month rats was oxidized in vitro. These results i ndicate: 1) that PMCA activity in SPMs from longer lived F344/BNF1 hybrids also decreases with age; 2) that part of the reduction in PMCA activity is due to loss of PMCA from the membranes; and 3) that age-related structural changes in CaM may decrease its interaction with proteins in SPMs. (C) 1998 Elsevier Science Inc.