Phosphate depletion increases cytosolic calcium of brain synaptosomes.
Phosphate depletion (PD) is associated with a rise in resting levels of [Ca2+]i in pancreatic islets. It is not known whether this derangement occurs in other cells, and the mechanisms by which PD affects [Ca2+]i have not been delineated. This study examined the effect of PD on [Ca2+]i of brain synaptosomes and evaluated potential mechanisms that may lead to rise in their [Ca2+]i. [Ca2+]i levels in synaptosomes of PD rats (460 +/- 18.3 nM) were higher (P less than 0.01) than those of pair-weighed (PW) rats (358 +/- 12.5 nM). Verapamil treatment of PD rats (PD-V) normalized [Ca2+]i in their synaptosomes (361 +/- 8.5 nM). In verapamil-treated PW rats (PW-V), synaptosomal [Ca2+]i (359 +/- 8.3 nM) was not affected. ATP content and Na(+)-K(+)-ATPase activity of synaptosomes were lower (P less than 0.01) in PD rats than in PW, PD-V, and PW-V rats. The values of these parameters from the latter three groups were not different. Km of synaptosomal Ca2(+)-ATPase was not affected by PD but Vmax of this enzyme (2.5 +/- 0.33 mumol Pi.mg protein-1.h-1) was lower (P less than 0.05) than in PW (5.4 +/- 0.66 mumol Pi.mg protein-1.h-1), PD-V, and PW-V rats. Our data indicate that PD raises [Ca2+]i in brain synaptosomes and suggest that PD increases calcium entry into synaptosomes. This would inhibit mitochondrial ATP production, with a consequent fall in ATP content of synaptosomes.(ABSTRACT TRUNCATED AT 250 WORDS)
Massry
S G
SG
Division of Nephrology, University of Southern California School of Medicine, Los Angeles 90033.
Hajjar
S M
SM
Koureta
P
P
Fadda
G Z
GZ
Smogorzewski
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D001923:Brain Chemistry; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D010710:Phosphates; D000255:Adenosine Triphosphate; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium