Aluminum alters calcium transport in plasma membrane and endoplasmic reticulum from rat brain.
Calcium is actively transported into intracellular organelles and out of the cytoplasm by Ca2+/Mg(2+)-ATPases located in the endoplasmic reticulum and plasma membranes. We studied the effects of aluminum on calcium transport in the adult rat brain. We examined 45Ca-uptake in microsomes and Ca(2+)-ATPase activity in microsomes and synaptosomes isolated from the frontal cortex and cerebellum of adult male Long-Evans rats. ATP-dependent 45Ca-uptake was similar in microsomes from both brain regions. The addition of 50-800 microM AlCl3 resulted in a concentration-dependent inhibition of 45Ca-uptake. Mg(2+)-dependent Ca(2+)-ATPase activity was significantly lower in synaptosomes compared to microsomes in both frontal cortex and cerebellum. In contrast to the uptake studies, AlCl3 stimulated Mg(2+)-dependent Ca(2+)-ATPase activity in both microsomes and synaptosomes from both brain regions. To determine the relationship between aluminum and Mg2+, we measured ATPase activity in the presence of increasing concentrations of Mg2+ or AlCl3. Maximal ATPase activity was obtained between 3 and 6 mM Mg2+. When we substituted AlCl3 for Mg2+, ATPase activity was also stimulated in a concentration-dependent manner, but to a greater extent than with Mg2+. One interpretation of these data is that aluminum acts at multiple sites to displace both Mg2+ and Ca2+, increasing the activity of the Ca(2+)-ATPase, but disrupting transport of calcium.
Mundy
W R
WR
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Kodavanti
P R
PR
Dulchinos
V F
VF
Tilson
H A
HA
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats
D017607:Aluminum Compounds; D002712:Chlorides; D000077410:Aluminum Chloride; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium